MUSC teams up for new clinical trial see more
A combination of up to five drugs normally used to treat conditions ranging from HIV to Type 2 diabetes could destroy cancer cells yet be less toxic than a chemotherapy drug used for recurring ovarian cancer.
After promising preclinical results, researchers at MUSC Hollings Cancer Center are now launching a phase 1 clinical trial to establish safe levels of various combinations of the drugs in patients with advanced solid tumors.
Hollings researchers Joe Delaney, Ph.D., and Michael Lilly, M.D., are collaborating on the Combination of Autophagy Selective Therapeutics (COAST) trial, which already has enrolled its first patient.
Autophagy is a cellular recycling process that occurs in all human cells, Delaney explained. Although the drugs in question – hydroxychloroquine, nelfinavir, metformin, dasatinib and sirolimus – were developed to treat, respectively, malaria, HIV, Type 2 diabetes and chronic myeloid leukemia and to prevent organ rejection in kidney transplant patients, what they all have in common is that they affect this cellular recycling process.
“All the drugs on this trial affect autophagy in one way or another. Even though they were originally designed for these other diseases, we’ve learned from the decades of studying them that they actually impact this process of autophagy, which all human cells have,” Delaney said. “That’s true of our normal cells. And that’s also true of cancer cells. It’s just that the cancer cells cannot perform that recycling nearly as well as our normal cells can. And so, to us, that was our therapeutic window.”
The National Cancer Institute encourages researchers to look into repurposing approved drugs, Lilly said. Already approved drugs have established safety records, whereas many potential new cancer drugs fail in early trials because they’re too toxic, Delaney said.
Repurposed drugs, on the other hand, have already been used by potentially millions of patients. “It really puts you many years ahead in the developmental pathway,” Lilly said.
In a paper published in June in Frontiers in Toxicology, Delaney showed that 14 doses of these five drugs were less toxic than Doxil, a chemotherapy drug used to treat ovarian cancer, multiple myeloma and AIDS-related Kaposi’s sarcoma. Now, the phase 1 trial will show safety levels in humans.
“We’re really enthusiastic that this might be that opportunity to try multiple drugs,” Delaney said. “Since we started from that side effect profile to begin with, hopefully we have something that has much less toxicity. And of course, we’ll be finding out in the coming months if that’s actually true or not.”
The drugs will be tested in a series of various combinations. Previous studies of drugs that target autophagy have mostly focused on adding one autophagy drug to a chemotherapy regimen or immunotherapy regimen, Lilly said. By combining multiple autophagy-targeting drugs, this trial hopes to identify a combination that prevents the cancer cells from evolving resistance to the drugs.
“We have very good evidence that it’s a synthetic lethal combination for cancer cells, which is what everybody in cancer wants, but it’s just never been tried in people before. And so, we’re really excited to see this combination in a cancer setting,” Delaney said.
Synthetic lethality refers to when mutations in two genes together result in cell death, but a mutation in only one of the partner genes does not.
This human trial is a result of work in the lab that was funded by both the National Cancer Institute and donor Matt Prisby, who established a fund at Hollings for research into women’s cancers after his wife died of cervical cancer in 2014.
“This trial couldn’t have happened without Matt Prisby and everyone who donated to his fundraisers,” Delaney said. “Dedicated funding programs like the one he established at Hollings are critical for investigators to get the early results that will convince large funding entities to invest in continued research along these lines.”
Delaney also hopes that a combination of these drugs will prove effective for a broad swath of patients. Operating within the concept of precision oncology, researchers have been looking for ways to target mutations in patients whose tumors have been sequenced. Yet fewer than 10% of patients are eligible for precision therapy, Delaney said, referring to an area of medicine that uses information about a patient’s own genes to develop specific treatments that, in terms of cancer, target that individual’s tumor.
This trial targets aneuploid gene changes – an extra or missing chromosome – which is common in cancer cells, ranging from 20% to 95% in advanced solid tumor patients.
“If it works, many, many more patients could be eligible than for other targeted therapies,” Delaney said.
The phase 1 trial is accepting patients with an advanced solid tumor of any type. Once the trial moves to phase 2, the researchers will focus on specific cancer types. Lilly said early indications are that these drugs might be particularly effective against ovarian and prostate cancers.
Lilly, who treats patients with prostate cancer and runs his own lab focused on advanced prostate cancer, said that this collaboration with Delaney would only be possible at an academic cancer center like Hollings, where researchers work alongside the doctors who provide care to patients. Delaney and Lilly, each with their own areas of expertise, can share ideas, and patients have access to early trials like this.
“Sherlock Holmes once referred to bits of data as having cumulative force when you have three or four different things, each of which points in the same direction,” Lilly said. “And that’s the power of collaborative research at Hollings.”
The first video shows high-grade serous ovarian cancer cells grown in the lab and labelled with fluorescent proteins to measure how the molecular recycling process of autophagy is working in live cells.
When the movie starts, the cells had just begun a treatment of a version of COAST therapy. As the movie progresses, the cells try to turn on autophagy in response to these COAST drugs - they fluoresce brighter.
However, properly recycling autophagy would fluoresce red, whereas these cells fluoresce yellow, indicating their recycling system is jammed and cannot complete its function. As a result, these cancer cells accumulate too much cellular debris and pop, as seen by a sudden darkening of a single cell.
The second video shows high-grade serous ovarian cancer cells grown in the lab and labelled with fluorescent proteins that label the nucleus of each cell in both green and blue.
In the center top of the start of the movie, a cancer cell physically latches onto another cancer cell. Astonishingly, the cell is able to absorb the blue nucleus of this attached cell, thereby adding a whole extra genome to its own genome in the process. This is a live observation of one reason why cancer cells can evolve to resist chemotherapy: once they acquire that second genome, it is easier to shuffle genes around in a way that optimizes cancer cell growth.
MUSC Shawn Jenkins Children’s Hospital achieves top rankings in annual U.S. News & World Report’s Best Children’s HospitalsMUSC SJCH only children’s hospital in South Carolina to be ranked see more
New rankings from U.S. News & World Report’s (USNWR) 2022-23 Best Children’s Hospitals survey place the MUSC Shawn Jenkins Children’s Hospital once again as the only children’s hospital in South Carolina to be ranked. And, the hospital improved one ranking, to #11, in the Southeast region best children’s hospitals survey. The latest rankings are published online and indicate the herculean efforts health care workers provided during the second year of the coronavirus pandemic.
The highly recognized specialties for MUSC SJCH include the following national rankings: No. 4 for cardiology & heart surgery, No. 30 for nephrology, No. 31 for cancer and No. 41 for gastroenterology & GI surgery. This year, the MUSC Pediatric & Congenital Heart Center received the #1 spot in the nation ranking for outcomes. This phenomenal achievement recognizes that the pediatric and congenital heart center’s expected outcomes are the best in the nation. USNWR issues the annual rankings “to help families with complex and rare conditions find the best medical care for their children,” according to the publication’s website. They’re designed to steer parents and caregivers to the hospitals that are best equipped to treat their children.
The 16th annual rankings highlight the top 50 U.S. pediatric hospitals in each of 10 specialties: cancer, cardiology & heart surgery, diabetes and endocrinology, gastroenterology and GI surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology and urology.
“The U.S. News rankings recognize on a national stage that MUSC Children’s Health is a leader in pediatric health care and a safe and compassionate choice for parents seeking care for their child,” said Mark A. Scheurer, M.D., MUSC Children’s Health chief of clinical services.
This is the 15th consecutive year that the 4th-ranked cardiology & heart surgery program has made the overall Best Children’s Hospitals list. Criteria include the survival rate of patients after complex heart surgeries along with the level of specialized staff, services and technologies and the ability to prevent infections.
The nephrology program at the MUSC Shawn Jenkins Children’s Hospital ranks No. 30 in the U.S. That means it excels when it comes to the survival rate of children who have had kidney transplants, the management of dialysis and infection prevention and other factors. It maintains its status as the highest-ranked children’s kidney program in South Carolina. The program ranked #3 in the Southeast for overall care and the third best outcomes.
The GI & GI surgery program is no stranger to the U.S. News rankings, either. For the 15th year in a row, it made the grade, coming in at No. 41, one spot higher than last year. The rankings factor in the survival rate for children who have had liver transplants, the effectiveness of the hospital’s treatment of children who have inflammatory bowel issues and other key measures. Like all of the rankings, the GI rankings also include input from specialists in the field who responded to U.S. News surveys and recommend the hospital for serious cases in GI care. GI & GI Surgery ranked #8 in the Southeast region.
Finally, the MUSC Shawn Jenkins Children’s Hospital’s cancer program ranks No. 31 on the list of Best Children’s Hospitals for Cancer. That’s a 13-level increase from last year’s ranking and a direct result of the #15 national ranking in outcomes. Cancer ranked #3 in the Southeast for overall care and achieved the best outcomes in the region. These rankings are based in part on the five-year survival rate for children with leukemia-related cancer, bone marrow transplant services, programs for brain tumors and sarcomas and infection prevention.
A critical criterion measured by USNWR is outcomes. Five of 10 MUSC Shawn Jenkins Children’s Hospital programs placed in the top 50 nationally for the outcomes portion of their respective survey, including:
GI / GI Surgery #37
For the second year, U.S. News featured regional rankings, and the MUSC Shawn Jenkins Children’s Hospital tied at #11 for the Southeast region, which is one of the most competitive pediatric regions in the country. Four of MUSC’s pediatric specialties ranked in the top 10: cardiology & cardiac surgery #1, cancer #3, nephrology #3, and GI & GI surgery #8.
Current methodology combines clinical and operational data, results from a reputational survey of board-certified pediatric specialists and supplemental information from resources such as the National Cancer Institute. RTI International collects and analyzes the data for the rankings. The methodology reflects clinical outcomes, such as patient survival, infection rates and complications; the level and quality of hospital resources directly related to patient care, such as staffing, technology and special services; delivery of health care, such as programs that adhere to best practices and prevent infections; and expert opinion among pediatric specialists. This year, scoring also included an increased focus on the subjects of diversity, equity and inclusion efforts; internal and external affiliations of experts; and clinical issues related to the pandemic.
“Our MUSC Shawn Jenkins Children’s Hospital care team members continue to be recognized for the outstanding care, service and commitment they provide, even in challenging times,” said Patrick J. Cawley, M.D., MUSC Health CEO and executive vice president for Health Affairs, University. “The strength of our specialty outcomes is a testament to the quality of care our team members seek to provide to patients and their families on a daily basis.”
Kiyatec invited to present at prestigious conference see more
Kiyatec, a leader in functional precision oncology, announced new clinical evidence of its proprietary ex vivo 3D cell culture technology use in high-grade glioma will be presented at ASCO 2022. As a first-time ASCO presenter and exhibitor, Kiyatec will present its Clinical Services and Drug Development Services capabilities at ASCO’s first-ever Innovation Hub at kiosk #IH01. The ASCO meeting will be held in Chicago June 3-7, 2022.
In this updated cohort of 42 patients with high grade glioma, 3D Predict™ Glioma prospectively predicted patient response to standard of care temozolomide (TMZ), regardless of MGMT methylation status. In a subgroup analysis of the 23 MGMT unmethylated patients, test-predicted responders had a relative median progression-free survival advantage of 5.9 months versus test-predicted non-responders (p = 0.0018). This data provides additional evidence of 3D Predict™ Glioma predictivity and its potential to provide additional information for glioma patient treatment options including clinical trial enrollment, alternative therapies indicated for use in glioma or combination therapy with TMZ.
Kiyatec Chief Executive Officer Matthew Gevaert, PhD, said, “This enhanced cohort adds to our body of clinical evidence demonstrating the predictive insights 3D Predict™ Glioma can provide to neuro-oncologists planning treatment for glioblastoma patients. With it, we’ve advanced our mission is to disrupt cancer care by accurately predicting patient-specific response and non-response before treatment begins.”
High grade gliomas, including glioblastoma, are among the most aggressive brain cancers, with patients exhibiting highly variable treatment responses in both newly diagnosed and recurrent disease. TMZ with radiation therapy is the guideline-directed standard of care in the newly-diagnosed setting, which has remained relatively unchanged for over 15 years despite variable patient responses.
Kiyatec’s ex vivo KIYA-Predict™ pre-clinical platform and 3D Predict™ clinical assays are leading the functional precision oncology space with published, clinically-correlated evidence to prospectively predict glioma patient therapeutic response prior to initiation of therapy.
Clinical application of a functional 3D ex vivo test to predict therapeutic response in patients with HGG: A progression-free survival analysis
Central Nervous System Tumors
Sunday June 5 8:00 – 11:00am
Abstract ID 2031
Kiyatec is a functional precision oncology company that measures the response of each patient’s live cancer cells to inform oncologists’ treatment selection decisions. The company’s Clinical Services offers clinical testing for high-grade glioma, and is developing assays for use in ovarian, breast, non-small cell lung cancers, and rare tumors in its CLIA-certified lab. The company’s Drug Development Services works in partnership with leading biopharmaceutical companies to unlock response dynamics for their pre-clinical investigational drug candidates across the majority of solid tumor types. For more information, visit www.kiyatec.com and connect with us on LinkedIn and Twitter.
Program aims to provide more access to rural, underserved areas see more
Improving health care access and rural and underserved populations across South Carolina is a priority of MUSC Health. A new program called Healthy Me – Healthy SC launched in 2019 to address these issues and has already succeeded in bringing health care services to more South Carolinians.
Healthy Me – Healthy SC is now planning to extend its reach even further. On this episode of Advance with MUSC Health, Kapri Kreps Rhodes and David Sudduth, director and executive director of Healthy Me – Healthy SC, join the show to discuss these new developments and share a bit more about this innovative program.
Improvements may one day improve the effectiveness and safety of chemotherapy see more
For patients with cancer, the tumor-killing power of chemotherapeutic drugs is a double-edged sword. While many cancer drugs kill tumor cells, they can also harm healthy cells as they travel throughout the bloodstream.
“A major limitation of chemotherapy agents is that only a tiny fraction goes to their targeted tumor,” said Dieter Haemmerich, Ph.D., D.Sc., professor at the Darby Children’s Research Institute within the Department of Pediatrics at the Medical University of South Carolina (MUSC). “As a result, there are side effects that include damage to the heart.”
But what if you could “cleanse” the blood of chemotherapeutic drugs to reduce their harmful side effects?
In an article published in March 2022 in the journal Cancers, an MUSC research team led by Haemmerich reported that it had developed a device to remove excess chemotherapeutic drugs from circulation after cancer treatment. Using this device, the team removed 30% of the administered drug by one hour after treatment. Seed funding to develop the device was provided by a High Innovation - High Reward grant from the South Carolina Clinical & Translational Research Institute’s pilot project program.
Haemmerich and his colleagues, including Katherine Twombley, M.D., a professor in the MUSC Department of Pediatrics, Division of Pediatric Nephrology, focused on doxorubicin (DOX), which is one of the most widely used chemotherapy drugs in adults and children.
DOX is also known to be toxic to the heart. This toxicity is particularly detrimental in pediatric patients, since any resulting heart failure will have negative health effects for the rest of the child’s life. In a 2006 clinical trial, DOX reduced cardiac function in children with leukemia, and steroid therapy was required to reduce its damaging effects.
Despite its toxicity to the heart, DOX is a popular chemotherapy drug because it is highly effective at stopping cancer cells from dividing.
“Doxorubicin works by basically damaging DNA,” said Yuri Peterson, Ph.D., an associate professor in the Department of Drug Discovery and Biomedical Sciences in the MUSC College of Pharmacy and an author of the article. “That is useful for treating cancer, but it can also cause off-target side effects like hair and bone marrow loss.”
Recent efforts to target DOX more precisely to the tumor site have included encapsulating it inside temperature-sensitive nanoparticles. These tiny particles are intact at normal body temperature and carry the drug through the bloodstream to the tumor. There, they can be heated with a probe to around 105 degrees Fahrenheit to release their DOX cargo.
However, the technique has its own limitations. Only a fraction of the administered nanoparticles release their cargo when the heat is applied at the tumor site. Once the nanoparticles break down in the body, which can take as little as an hour, the remaining drug enters the bloodstream and can then cause side effects.
The MUSC research team wanted to improve outcomes with this technique by developing a device that would remove the leftover DOX after treatment.
Using a rodent model of cancer, the researchers injected the heat-sensitive DOX nanoparticles and applied heat at the tumor site to release DOX. After treatment, they cleansed the blood of leftover DOX by first passing it through a heating element to get the nanoparticles to release the drug and then through an activated carbon filter to remove the drug from the blood before it was returned to the rodents’ circulation.
Krishna Ramajayam, Ph.D., a postdoctoral fellow in Haemmerich’s laboratory in the Division of Pediatric Cardiology at MUSC, designed the heating element in the filtration device and supported the imaging studies for monitoring drug release and filtration.
“Since the device is computer controlled, you can have very precise heating to ensure that the drug is released,” said Ramajayam. “The most exciting part for me is addressing both delivery and removal of the drug, which will improve patients’ quality of life immensely.”
Importantly, the team also developed a method for detecting drug levels in the blood in real time to ensure that the drug is effectively removed.
“By imaging the blood before and after filtration, we can actually predict how much drug is being removed in real time in the clinic,” said Anjan Motamarry, Ph.D., who completed work on the study while a doctoral student in Haemmerich’s lab before transitioning to a job in industry. “This would be very useful information for a clinician who needed to make a decision about when to stop filtration.
”Reducing the exposure of patients to leftover chemotherapy drugs could allow them to recover faster, with fewer side effects. It could also enable them to receive more chemotherapy cycles in the future in case additional treatment is necessary to kill the cancer cells.
“Every drug has a maximum tolerated dose that you cannot go beyond,” said Motamarry. “Since we are removing the leftover drug after treatment, you can actually give an additional dose if the first cycle is not sufficient, which would not be possible if the drug was not removed.”
Filtering the blood through the device also led to nearly three times less DOX in the heart, as measured using mass spectrometry at the MUSC Drug Discovery Core. Peterson and Thomas Benton, Ph.D., who was a doctoral student at MUSC at the time of the study, performed the measurements.
These promising results suggest that the new device could reduce side effects in the heart that can be caused by chemotherapy, but more studies will be needed to confirm that promise.
“If you deliver less drug to the heart, you will probably have fewer side effects,” said Haemmerich. “Our next step is to test the function of the heart directly after using this method in long-term animal tumor studies.”
Further improvements to their device may one day improve the effectiveness and safety of chemotherapy in children and adults.
“It’s really hard for anyone to go through chemotherapy,” said Motamarry. “This is the least that we can do to make it easier for them.”
MUSC ranked #30 among public institutions see more
The Medical University of South Carolina College of Medicine has been ranked No. 56 in Best Medical Schools: Research by U.S. News & World Report’s latest survey. The school tied with Georgetown University.
When ranked solely among other public institutions, MUSC came in at No. 30.
The U.S. News research rankings are based on federal expenditures, survey assessments completed by deans and senior faculty members at peer institutions, and entering class data, MUSC said. The magazine surveyed 192 accredited medical and osteopathic schools in the U.S. for this year’s rankings.
“This ranking is truly a testament to the dedication of our faculty, their leadership and their desire to make discoveries that can change the lives of patients,” said Lisa Saladin, MUSC executive vice president for Academic Affairs and provost. “Research is at the core of what we do as an academic health sciences center, and we believe it is an important component of medical education. Our faculty, students, trainees and staff are inspired to reach for the impossible every day, which is vitally important in a time where we’re more committed than ever to improving the health of all.”
MUSC was additionally recognized by U.S. News & World Report as nationally ranked in several adult specialties, including No. 17 in gynecology, No. 14 in ear, nose and throat and No. 39 in cancer. The institution also was ranked No. 6 in most graduates practicing in medically underserved areas.
In the most recent Best Children’s Hospitals Honor Roll, MUSC also ranked in pediatric specialties, including No. 12 in cardiology and heart surgery, No. 30 in pediatric nephrology, No. 42 in pediatric gastroenterology and gastrointestinal surgery and No. 44 in cancer.
KIYATEC expands team by adding two executives see more
KIYATEC, the leader in clinically correlated, published functional precision oncology technology today announced two key appointments as the Company builds utilization of clinical 3D Predict™ assays and grows its pharmaceutical services portfolio for KIYA-PREDICT™. KIYATEC is pleased to welcome Bruce Yeager as Vice President Market Access & Reimbursement effective March 21, 2022, and Steven Holshouser, Ph.D., as Director, Business Development, effective March 8, 2022.
Chief Executive Officer Matt Gevaert, Ph.D., said, “We are pleased to welcome both Bruce and Steven to our growing team of experienced leaders in their respective fields. Bruce’s significant experience and effectiveness in securing and expanding Medicare and private payer reimbursement and coverage will support the commercialization of 3D Predict™ Glioma and Ovarian assays in 2022 and lays the foundation for reimbursement and coverage plans for our non-small cell lung, rare tumor, and breast cancer assays in the future. Steven’s track record in securing pharmaceutical services contracts will expand revenues from our growing portfolio of clients using KIYA-PREDICT™ therapeutic response and 3D cell culture technology applications in their drug development plans.”
KIYATEC’s clinical and pre-clinical technology platforms, 3D PredictTM and KIYA-PREDICTTM, respectively, are leading the functional precision oncology space with published evidence of predictive response correlated to clinical outcomes. Recently the Company represented its 3D Predict™ Ovarian publications at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and announced six abstract acceptances to be presented at the American Association for Cancer Research from April 8-13, 2022 in New Orleans.
KIYATEC is a functional precision oncology company that measures the response of individual patient live cancer cells with its innovative 3D cell culture technology platform. The Company offers clinical tests for high-grade glioma and is developing tests for ovarian, breast, non-small cell lung and rare tumors in its CLIA-certified lab. The Company works with leading biopharmaceutical companies to unlock response dynamics for their investigational drug candidates across the majority of solid tumor types. For more information, visit www.KIYATEC.com and connect with us on LinkedIn and Twitter.
Exosomes have been called the rising star of drug delivery see more
Terri Bruce happened to be working on experiments about how the body’s cells communicate when her brother learned he had a brain tumor. Greg Foster died in January 2019, within months of Bruce starting a company whose work could soon help save other cancer patients.
“When he got sick, I started looking at how exosomes could be used in early cancer diagnostics,” the Clemson University researcher and entrepreneur says. “Had we caught it a little bit earlier, he may have been able to receive treatment that might have saved his life.”
So … what is an exosome?
For 40-odd years, scientists considered exosomes waste materials. Miro Pastrnak, Bruce’s partner in their startup, Victory ExoFibres, describes them as “sneeze droplets for cells.” Bruce calls exosomes “messages in oil balls,” which carry disease markers in common body fluids. Unlike cell-free DNA or proteins that degrade rapidly, exosomes’ lipid casings protect those markers in biofluid.
The trick is to efficiently isolate them. The company uses patented synthetic fibers to do just that.
Requiring less than a milliliter of bodily fluid, each isolation container contains a tube that looks like a golf tee. Inside that tube is the patented fiber that isolates the exosomes. When spun in a lab centrifuge, the exosomes are now ready to give up their secrets.
The process takes about 15 minutes. Until now, extracting these molecular spies could take up to four hours, Bruce and Pastrnak say.
“It’s like trying to pick peas out of your mom’s vegetable soup, that you don’t want to eat. There’s a lot of stuff in that veggie soup, but to look at those peas specifically you’ve got to get them out of the veggie soup,” Bruce says.
The Clemson assistant research professor, who earned her doctorate in biological sciences from there in 2009 after working as a chemical engineer for the likes of Duracell and Lockwood Greene, explains the product’s multiple benefits.
Typically, testing for or, worse, diagnosing cancer is invasive, Bruce says: “You often have to go into an operating room or sterile area to get this done.” That’s why Bruce and Pastrnak refer to Victory ExoFibres’ product as a liquid biopsy, which, she says, is also “just generally more pleasant for the patient.”
Each kit holds 50 exosome-isolation tubes. For each box, the target price will fall between $500 and $700 for the product, which Pastrnak expects to hit the research-supplies market in the next few months.
Ultimately, the company hopes to include exosome-based clinical diagnostics, but that requires FDA approval, a process that can cost more than $10 million. Once the company validates the product in the market, Pastrnak says fundraising will begin in earnest.
Victory ExoFibres won an early backer, the South Carolina Research Authority, which in January accepted the company as a member. That opens the door to SCRA’s Resource Partner Network and potential investments from authority affiliate, SC Launch Inc.
“The work that Victory ExoFibres is doing is critical to the future of health care,” SCRA program manager Jeannine Briggman Rogers says. “Any advancement in the accuracy, speed and clarity of diagnostic testing that improves the quality of patient care benefits everyone.”
Bruce credits her brother with infusing his experience as a founder of two tech startups, an executive at Turner Broadcasting System and as a venture capitalist, into her scientific-cum-corporate enterprise.
Foster died at 45 in their native Atlanta. Catching brain and ovarian and other such cancers can result in higher remission rates, Bruce says. That, and her brother’s encouragement, continue to drive and inspire her.
“I’m going to keep going, keep going,” she says. “Those are discussions that my brother and I used to have and that’s one thing I really miss about him.”
What are Exosomes?
“Exosomes are a perfect target for rapid diagnostics and liquid biopsy,” the company says, explaining that they are formed from the plasma membrane of cells:
They contain the same membrane proteins as the host cell.
These proteins are “fingerprints” that can be used as disease biomarkers in diagnostics.
They are cellular couriers that genetic information between cells.
Virtually every cell type in the body releases these biomolecules.
Exosomes have been called “the rising star in drug delivery.”
Innovative ostomy care company plans to add at least 30 new jobs, make “significant investment” see more
Stomagienics, Inc., a company that provides innovative solutions for cancer survivors and others who have undergone ostomy surgery, today announced expansion of operations in Greenville County. The company’s undisclosed investment is expected to result in growth including creation of 30 new jobs over 3 years.
“The support and resources made available to us through state and local programs, along with outstanding private sector talent, have been instrumental in our development, and make Greenville, South Carolina a great place to start and grow a business,” said Theresa Johnson, Co-founder and COO of Stomagienics. “We have gained access to project grants, intellectual property development, Medicare reimbursement expertise and connections to leading universities, clinical staff, and life sciences professionals. Our partnerships with SCBIO, GADC, SCRA and NEXT are all positive factors as we seek capital to reach the next level in our development.”
Launched in 2018, Stomagienics is committed to delivering products that are easy-to-use and essential to ostomy care. The founders realized the enormous gap in ostomy care when a family member had ostomy surgery and entered a deep depression. The lack of control over stoma output led to the company’s patented StomaGenie pouch replacement cartridge, which gives ostomy patients control of output and allows for a hygienic and sanitary experience.
“When a homegrown company experiences success within our borders, all of South Carolina wins. We are particularly proud of the fantastic work Stomagienics is doing every day to improve the lives of people around the world. We congratulate Stomagienics and look forward to many more years of their success,” said South Carolina Gov. Henry McMaster.
Located in expanded facilities at 1200 Woodruff Road in Greenville, Stomagienics’ expansion includes facilities and equipment for sales and operations, production of its StomaGenie pouch replacement cartridge, and research and development investment.
“South Carolina’s life sciences industry is booming, and today’s announcement by Stomagienics in Greenville County is just the latest example,” noted Secretary of Commerce Harry M. Lightsey III . “Their expansion not only proves that South Carolina has the business environment where life sciences companies can succeed, but that we have the talented workforce in place to handle the most innovative jobs.”
With a mission to improve the lives of ostomy patients everywhere by helping them manage their ostomy, the Stomagienics team created a revolutionary device for pouch replacement that has helped many patients return to a more normal life. Stomagienics also found a ready market for its innovative product. More than 35% of ostomy patients experienced a peristomal skin complication during the first 90 days after surgery, while over 80% experience some type of complication within two years of their surgery – driving up costs and impacting patient outcomes.
“It is particularly rewarding when a home-grown organization like Stomagienics chooses to grow and expand its presence in Greenville County, said Willis Meadows, County Council Chairman and Greenville Area Development Corporation Board Member. This is evidence that our strategic focus on helping existing industry grow is paying off, and that our strategic emphasis on medical devices and life science organizations are producing results. We congratulate Stomagienics on this major step forward and wish them continued success into the future.”
The Stomagienics solutions improves hygiene, promotes better skin health and condition, and enhances patient independence and self-confidence, the company reports. The company is dedicated to continuing innovation initiatives to create and produce new and advanced solutions for ostomy care.
Stomagienics is actively pursuing distributors, investors and business partners. Individuals interested in learning about or supporting Stomagienics’ mission should email the company at firstname.lastname@example.org, or visit them on the web at www.stomagienics.com.
The Greenville Area Development Corporation is a non-profit organization established by Greenville County Council to promote and enhance the economic growth and development of Greenville County. Since its founding in 2001, GADC efforts have resulted in the creation of over 30,000 new jobs, nearly $6 billion in capital investment, and a cumulative economic impact of over $55 billion in Greenville County, SC -- including an economic impact of more than $6 billion annually. To learn more, please visit www.goGADC.com or call (864) 235-2008. To learn more about workforce opportunities, visit www.jobsingreenvillesc.com.
MUSC helping create new hope for cancer patients see more
As a 10-year journey comes to fruition, MUSC Hollings Cancer Center researcher John O’Bryan, Ph.D., and colleagues have demonstrated a new therapeutic way to block a protein that is frequently mutated in cancers. These proof-of-principle findings were published on Feb. 8 in Cell Reports. This work, which involves inhibiting the oncogenic protein RAS using small molecules, lays a strong foundation for the development of clinical anti-cancer therapies.
The American Cancer Society estimates that 1.9 million new cancer cases will be diagnosed this year. Based on the urgent need for more effective therapies, researchers are always on the search for elusive treatments that can affect many cancers.
O’Bryan, who is a professor in the Department of Cell and Molecular Pharmacology and Experimental Therapeutics at the Medical University of South Carolina, said, “RAS is one of the most central and critical regulators of cell proliferation, and it is also the most mutated in cancers. Mutated RAS drives the growth of tumors. This makes it an attractive therapeutic target.”
The RAS family of proteins are mutated in nearly 20% of human tumors; however, there has been little progress in drug development for this target. “Think of RAS as a slick ball that does not let anything bind to it. Until recently, it was thought that mutant RAS could not be targeted with drugs. Now there is one FDA-approved drug for mutant RAS in lung cancer, which demonstrates that it is possible to target mutant RAS in some cases,” said O’Bryan.
The new drug sotorasib targets a mutant form of RAS that only occurs in less than 3% of all human cancers, so the new drug is not very useful across multiple types of cancers, O’Bryan said. His new method of therapeutically targeting mutant RAS is more promising because it has the potential to work with numerous mutant forms of RAS in multiple cancers.
“Pancreatic, lung and colorectal cancers are three of the four most deadly cancers, and their growth is driven by mutations in RAS proteins. Therefore, successfully targeting mutant RAS has big implications for patients,” said O’Bryan.
The challenge with targeting RAS is due to the way it functions. It has “on” and “off” states that are regulated by binding to other molecules called nucleotides. There is also a third state called the nucleotide-free state when it is switching between on and off modes. However, RAS proteins are in their nucleotide-free states for such short amounts of time that it was previously thought that RAS could not be targeted during this very short-lived state.
O’Bryan’s collaborator Shohei Koide, Ph.D., from the Perlmutter Cancer Center at New York University, developed the monobody technology that overcomes the challenges with targeting nucleotide-free RAS. Monobodies are small synthetic binding proteins that can be designed to attach to cellular targets inside or outside of cells. Previously, targeting nucleotide-free RAS mutants was thought to be an impossible undertaking.
Targeting nucleotide-free RAS with the R15 monobody has allowed the researchers to understand RAS biochemistry more fully and discover opportunities to disrupt its cancer-promoting activity. Using a mixture of biochemistry techniques, cell culture work and animal models, they found that the R15 monobody blocks multiple forms of RAS mutants.
“We were surprised to find that many RAS mutants unlock nucleotides, and the R15 monobody can block these,” said O’Bryan. “It is a good sign that more than 50% of oncogenic RAS mutants may be susceptible to inhibitors binding nucleotide-free RAS. This makes targeting nucleotide-free RAS a viable approach for inhibiting many mutant RAS-driven tumors.”
There is often serendipity in a research career, O’Bryan said. “We got stuck by our early data because it did not make immediate sense. However, it turned out to be an exciting finding. There is a skill in discerning between insignificant artifacts in the data and something novel that is real discovery.”
This work provides a framework for other groups to target RAS in more effective ways. “The RAS protein, which was considered undruggable, is in fact able to be targeted by drugs,” said O’Bryan.
The researchers are very hopeful that this discovery can be used more comprehensively in the future. While cancers do adapt and mutate to become resistant to therapeutics, new drugs based on this concept might serve as additional tools in the arsenal to treat cancer, he said.
The next step in the journey will be to find small molecules in MUSC’s compound library that can be used to target mutant RAS in the same way as the R15 monobody. Since the R15 monobody cannot easily get into cells, O’Bryan explained that a small molecule targeting nucleotide-free mutant RAS proteins will be a more effective therapy.
“We are at a really good stage to exploit this mechanism,” said O’Bryan. “MUSC and Hollings have a really great culture of collaboration, which has helped to push this project forward. MUSC’s access to the massive library of small molecules helps to provide a lot of chemical diversity and intellectual property potential.”
The researchers feel that this research reveals a new window of opportunity for the development of novel anti-cancer agents necessary to improve patient outcomes.
MUSC making its mark in cancer treatments see more
Many cancer treatments such as chemotherapy and radiation kill cancer cells by inducing significant DNA damage beyond repair. But some tumors still develop alternative ways to survive. Now, scientists at the Medical University of South Carolina (MUSC) and Beth Israel Deaconess Medical Center have identified such a molecular pathway that helps cancer cells evade destruction.
The protein ECT2 is critical for the activation of a backup survival mechanism cancer cells resort to as part of their response to DNA damage, the scientists described in a study published in the journal Science Signaling.
As DNA damage response is essential for cell survival or death, better understanding of its mechanisms could lead to better combination therapies that can overcome tumor resistance, three researchers at the University of Illinois Chicago (UIC) said in an accompanying editorial.
Scientists know that the kinase AKT is a key regulator of genome stability—hence cell survival—by mediating downstream signaling involved in DNA damage response and DNA repair. Increased activation of the enzyme has been linked to cancer progression and resistance to drugs. However, the exact mechanisms of AKT activation in the face of DNA damage were unclear.
For its study, the MUSC and Beth Israel team treated multiple cancer cell lines with ionizing radiation or the chemotherapy etoposide and examined their responses. The researchers found that in response to drug-induced DNA damage, the DNA-PK enzyme modified a subunit of the mTORC2 protein complex.
ECT2 recognized that interaction and subsequently promoted AKT activation, according to the team. When ECT2 was removed in cancer cells, treatment with etoposide didn’t induce AKT activation. Compared with control cells, these ECT2-depleted cells responded better to etoposide, showing decreased colony formation.
What’s more, reintroducing ECT2 to the cells enhanced AKT activity, while an ECT2 mutant failed to do so, the team showed. Between the two groups, cells expressing normal ECT2 were less sensitive to etoposide partly because of reduced cell death.
A cancer patient may go through multiple lines of treatment as cancer cells outsmart the drugs they encounter. Many research groups are exploring ways to render resilient tumors vulnerable to existing treatment. Last year, two teams of scientists demonstrated the promising effects of inhibiting an enzyme called POLQ on BRCA-mutated tumors that had stopped responding to traditional PARP inhibitors.
A research team at the Swiss Federal Institute of Technology in Lausanne recently proposed adding CSF1R inhibition to control tumor-associated macrophages as a strategy to restore responses to the combination of PD-1/L1 immune checkpoint inhibitors, antiangiogenic drugs and chemo.
“Targeting the [DNA damage response] in cancer is of great clinical importance to traditional, current and emerging therapies including immunotherapy given the observed induction of antitumor immunity by DDR-targeted therapies,” the UIC researchers wrote in the editorial.
Findings from the current study pointed to combining DNA damage with DNA-PK-ECT2-mTORC2 network inhibition as a more efficient therapy against cancer, they said.
New DNA-based approach may be wave of the future see more
If your doctor knew your risk for colon cancer or heart disease years before the disease developed, he or she could help you take steps to prevent it.
And by collecting DNA samples from thousands of South Carolinians, the Medical University of South Carolina is embarking on a project which hopes to do just that.
In the initiative, which stakeholders call the first of its kind in the state, MUSC is partnering with population genomics company Helix to study DNA to drive a concept known as precision medicine. It allows providers and patients to develop health care plans with a more preventive approach.
The power in precision medicine cannot be overstated, said Dr. Lori McMahon, vice president and associate provost for research at MUSC.
“Genes are what make us who we are,” she told Integrated Media, publisher of Greenville Business Magazine, Columbia Business Monthly and Charleston Business Magazine.
“What we learn here … will influence care for individuals across the country and across the globe.”
The earlier genes associated with a disease are found, the better the chances of successful treatment, said Dr. Dan Judge, professor of medicine and cardiology at MUSC and director of cardiovascular genetics.
Theoretically, this concept might have helped “Black Panther” star and Anderson, S.C., native Chadwick Boseman, he said.
Boseman died last year of colon cancer at the age of 43, seven years before traditional colonoscopy screening typically begins, he said.
Had he learned through DNA testing that he had a propensity to develop the disease, that screening could have begun much earlier, perhaps in time to keep the cancer from progressing, he said.
And a woman with a genetic predisposition to breast cancer might begin mammograms at an earlier age or get more sensitive MRIs instead, Judge said.
“We hope we’ll be saving lives with this project,” he said. “That’s really the bottom line.”
The project will focus on certain forms of cancer and cardiovascular disease initially, but hopes to expand to other diseases in time, McMahon said.
Called “In Our DNA SC,” the project hopes to enlist 100,000 South Carolina adults – 25,000 a year for four years, Judge said.
The initiative will start with MUSC patients who already have an electronic health record and an upcoming appointment, he said. They will get a message through MyChart to let them know they’re eligible. Later, it will expand across South Carolina.
“It won’t be something that private physicians can order directly,” he said. “This program requires people to sign up through a review board process so that it’s gone through protocol, and safety and confidentiality issues are all addressed.”
Similar programs have identified as many as one in 75 participants who were at risk for a serious health issue, 90 percent of which would not have been discovered through traditional practice, said Dr. James Lu, CEO and co-founder of California-based Helix, which describes itself as a population genomics company at the intersection of clinical care, research and genomics.
“By expanding access and making genomic data actionable for health care providers,” he said, “we will be able to work in tandem with MUSC … to identify risk earlier and prevent or mitigate serious diseases for its community and beyond.”
The popularity of companies like 23andme shows that people want to understand their genetics, McMahon said.
“People are even buying DNA kits for their dogs,” she said.
The genetic test is free to participants and involves only a saliva sample.
Genetic counseling will be provided to patients whose DNA reveals a risk for disease so there can be further discussion of what it means for the patient and for family members who might be at risk as well, he said.
In addition to the clinical component, the project has a research component that will develop a dataset to advance genomics research.
It also will examine how genetic changes influence the development and progression of disease, McMahon said, and help in the development of new and better therapeutics.
For instance, some people respond to certain blood pressure medications while others don’t, but it’s not understood why.
“This will help us try to understand the genetic basis for that,” she said, “and who may need alternate therapy.”
Caroline Brown, chief of external affairs at MUSC, said the hospital system and Helix took steps to ensure that patient data are secure. While the results are linked to the patient’s medical record so his provider has access to them, the information is de-identified for research purposes, she said.
The genetic results will be entered into the participants’ medical records, like a chest X-ray or MRI results are, where they are available to insurers, Judge said.
While there is a law called the Genetic Information Nondiscrimination Act that protects people from health insurance or employment discrimination on the basis of genetics, information in medical records can be used to deny life insurance or charge more for it, he said. Patients will be informed of that as part of the consent form for participation, he said.
Brown said that as a state academic medical center, MUSC is focused on building its genomics prowess to ensure it can be a leader in precision medicine in the future. It chose to partner with Helix because of its established data analytics platform which is capable of large-scale projects like this, she said.
“MUSC looked for a strategic partner to offer genetic testing that can be provided to the patient and his provider so they better know how their genetic makeup impacts their health,” she said.
MUSC has identified funding for the program, Brown said, but she declined to divulge the cost.
McMahon said that when patients and providers are armed with genetic information, they can make better decisions about care going forward and push health care to a new level.
“This is the way of the future,” she said.
And Judge said he expects it will likely be routine within 20 years.
Clemson researchers pursue cutting-edge science and targeted medicine to improve lifespan, quality see more
In the last 25 years, rigorous research, broad medical collaborations and lifesaving interventions have made huge strides for cancer treatment. That means survival rates are up across the board for almost all forms of cancer, including the two most common ones for South Carolinians: breast and prostate cancer.
As recently as the late 1990s, there were clinical trials, and there were heroic efforts, but there were very few effective treatments for combatting some of the most highly aggressive forms of cancer. Twenty-five years later, some of those same cancers have a more than 80 percent survival rate.
Clemson can point to health innovation through research that has played notable roles in improving health outcomes for patients statewide. And that’s because cancer intervention isn’t isolated to bedside care from a nurse or petri-dish analysis from the lab.
Today, cancer treatment is:
- Powered by huge data sets that build the artificial intelligence needed to identify root causes of and precision cures for cancer.
- Innovative approaches, such as precision radio frequency that targets cancer cells rather than an IV drip administering chemotherapy drugs.
- Cellular research to develop new methods of finding and eliminating cancer faster, more safely and more efficiently.
- Identifying and preventing the side effects of treatment drugs and improving quality of life for patients even as they and their health care teams aggressively fight cancer.
Expanded use of test builds on previous month’s publication of successful interim clinical data see more
Functional precision oncology innovator Kiyatec announced today that it is initiating use of the 3D Predict™ Glioma test outside of its 3D-PREDICT clinical study. Recently published peer-reviewed data demonstrated successful use of this test for patients with either newly diagnosed or recurrent high-grade gliomas, which includes glioblastoma (GBM).
In choosing July 21, 2021, to announce the expanded use of its test, KIYATEC joins the country in shining a light on glioblastoma, which is the most common, treatment-resistant, and deadliest type of brain cancer. A recent bipartisan U.S. Senate resolution declared today as Glioblastoma Awareness Day in order to highlight the severity of GBM, and show support for individuals who are currently living with GBM, as well as caregivers and families. Additionally, the resolution encourages continued investment into glioblastoma research and treatments.
“At the core of KIYATEC’s mission is the desire to improve cancer patients’ lives. We’re excited to take the next step in fulfilling this mission by expanding the use of our testing for patients with GBM, which is such an aggressive cancer with few treatment options,” said Lillia Holmes, Chief Operations Officer at KIYATEC.
In a patient, the biological interaction between their live cancer cells and the administered therapy drives treatment outcomes. Measurement of this interaction, before prescribing a treatment plan, is not typically part of today’s cancer treatment paradigm. KIYATEC’s test results add this measurement into the information that informs oncologists’ treatment decisions for a given patient. This approach translated to patient benefit while demonstrating clinically relevant accuracy, as documented in the June Neuro-Oncology Advances publication.
The 3D Predict™ Glioma test is designed to work within the current framework of standard of care for high-grade glioma patients. Since live cells are required for the test, a patient’s oncologist must sync sample submission with the timing of the first surgery for newly diagnosed patients, or recurrent surgeries for relapsed patients. Oncologists interested in the potential use of the test to inform their decision-making, or requesting test kits to provide samples, should contact the company at email@example.com.
“Our goal is to provide oncologists with a more effective decision-making tool, by combining individual patient’s cancer cells with potential treatment drugs,” said Stephen Shuford, first author on the company’s recent Neuro-Oncology Advances publication.
The Senate resolution recognizes that:
- The five-year survival rate for GBM patients is 7%,
- The median length of survival is 8 months,
- Approximately 13,000 Americans will be diagnosed with GBM in 2021,
- Brain cancer has the highest per-patient initial cost of care, and
- Despite being first described over a century ago, there are only four FDA approved drugs and one device for GBM.
KIYATEC aims to make a meaningful impact for patients who are facing this challenging cancer.
KIYATEC is a functional precision oncology company that measures the response of each patient’s live cancer cells to inform oncologists’ treatment selection decisions. The company’s Clinical Services business offers or is developing clinical tests for high-grade glioma, ovarian, breast, and non-small cell lung cancers, and rare tumors in its CLIA-certified lab. The company’s Drug Development Services business works in partnership with leading biopharmaceutical companies to unlock response dynamics for their investigational drug candidates across the majority of solid tumor types.
BridgeBio Pharma Announces Collaboration with MUSC Foundation for Research Development, 2 Other Research InstitutionsWill identify and advance therapies for genetic diseases and cancers see more
BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical company founded to discover, create, test and deliver meaningful medicines for patients with genetic diseases and cancers with clear genetic drivers, today announced three new academic collaborations with MUSC Foundation for Research Development, Stanford University and the University of Pittsburgh (Pitt) to translate cutting-edge discoveries into potential therapies for patients with genetic diseases and genetically driven cancers.
"The chance to partner with exceptional researchers at the Medical University of South Carolina, Stanford University and University of Pittsburgh is a privilege, and we believe will help us advance our mission to discover, create, test and deliver life-changing medicines for patients in need as rapidly as possible," said BridgeBio founder and CEO Neil Kumar, Ph.D.
To date, BridgeBio has worked with 23 leading institutions throughout the country that are focused on providing treatment options to patients as quickly and safely as possible. For a list of some of the institutions BridgeBio is partnered with, please visit Our Partners page.
MUSC Foundation for Research Development
MUSC Foundation for Research Development provides technology transfer services to Medical University of South Carolina (MUSC), which is a patient-centric research institution with several hospitals in South Carolina and is considered the state's top healthcare provider. MUSC's innovative and high-quality research will allow for early identification of research programs with a strong potential to be beneficial for patients. Through this partnership, BridgeBio may sponsor research programs and support the development of identified programs toward potential clinical investigation through its licensing and affiliate development model.
"Like BridgeBio, we have a patients first mentality, so partnering together on early research will be an excellent opportunity to advance our innovation in the hope of generating new therapies for patients," said Scott Davis, Ph.D., senior director of innovation support and commercialization of MUSC Foundation for Research Development.
About BridgeBio Pharma, Inc.
BridgeBio Pharma (BridgeBio) is a biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio's pipeline of over 30 development programs ranges from early science to advanced clinical trials and its commercial organization is focused on delivering the company's first two approved therapies. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com.