MSK Research Highlights, March 28, 2024

(Press-News.org) Low recurrence seen with cryoablation for large breast tumors Cryoablation, a minimally invasive technique used to freeze and destroy small tumors, is effective for breast cancer patients with larger tumors, according to research presented by MSK interventional radiologist Yolanda Bryce, MD, at the 2024 Society of Interventional Radiology Annual Scientific Meeting.

The retrospective study assessed outcomes for 60 patients who underwent cryoablation because they were not candidates for surgery or declined surgery due to other health concerns. The average size of their tumors was 2.5 centimeters. In a follow-up after 16 months, only 10% of patients experienced a recurrence of their cancer.

“For patients who have larger tumors but can’t undergo surgery, this approach could be more effective than the current standard of care for patients who are not surgical candidates,” Dr. Bryce said in news release from the meeting. “When treated with only radiation and hormonal therapy, tumors will eventually return. So the fact that we saw only a 10% recurrence rate in our study is incredibly promising.” in the society’s news release.

 

New targeted drug approved for metastatic non-small cell lung cancer On February 15, 2024, the U.S. Food and Drug Administration granted full approval to the targeted therapy tepotinib (Tepmetko®). Tepotinib is used to treat metastatic non-small cell lung cancer caused by a genetic error called METex14. The drug had previously received an accelerated approval in February 2021.

Tepotinib was approved based on the findings from a multicenter international phase 2 clinical trial known as VISION. MSK thoracic oncologist Paul Paik, MD, Clinical Director of MSK’s Thoracic Oncology Service, was lead author of the VISION study and treated patients on the trial, as initially reported in The New England Journal of Medicine. He also co-authored a follow-up study published in JAMA Oncology in September 2023 that reported the long-term outcomes of patients who participated in the VISION trial. The overall response rate for patients in the study was 51%. The study also found that, for the patients who responded to tepotinib, the drug continued to work for a long time. The average length of time that patients responded was 18 months, with those who had not received any previous treatments receiving even longer benefit. The most common side effects from tepotinib, which is taken daily as a pill, are swelling, gastrointestinal problems, decreased appetite, and changes in liver enzymes.

 

PGBD5 mutator causes common childhood brain tumors In 2017, a team led by MSK cancer biologist and pediatric oncologist Alex Kentsis, MD, PhD, made a surprising discovery: A gene called PGBD5 can trigger tumors when it becomes abnormally activated. The PGBD5 protein wreaks havoc on other genes in rhabdoid tumors, a lethal rare childhood cancer.

Now a new study by Dr. Kentsis’ team and collaborators from the Sloan Kettering Institute and other institutions, and led by Makiko Yamada, MD, PhD, and Ross Keller, PhD, shows that PGBD5 also causes medulloblastomas, the most common malignant brain tumor in children. Remarkably, PGBD5 is apparently essential to the tumors’ formation. The researchers showed that mouse models genetically modified to have no PGBD5 are largely protected from tumor formation — even when the researchers tried to cause tumors by introducing powerful cancer-causing mutations.

“This finding is a necessary first step in understanding the causes of tumors in young people,” Dr. Kentsis says. “We hope that understanding the mechanisms by which PGBD5 creates cancer-causing mutations may eventually lead to precise targeted treatments and possible screening and prevention strategies.” He points to one possible approach using drugs that block DNA-damage repair. Cells with activated PGBD5 become so overwhelmed with DNA damage that they self-destruct. This strategy has begun to be tested in clinical trials, including a recently completed phase 2 clinical trial for children with refractory solid tumors expressing PGBD5. in Science Advances.

 

Unlocking the secrets of natural killer cell metabolism Natural killer (NK) cells are unique in their ability to target and destroy cancer cells without requiring prior activation. Understanding the nuances of their metabolism is critical for the development of NK cell-based immunotherapies, since the environments around tumors are often starved of critical nutrients. A new study from the lab of Joseph Sun, PhD, at the Sloan Kettering Institute, reveals that a metabolic process called fatty acid oxidation is vital to NK cells, and that a key enzyme called carnitine palmitoyltransferase I (CPT1A) is critical to the immune cells’ ability to function well. “By uncovering the importance of fatty acid metabolism to NK cells, we hope to improve the ability to harness the power of these immune cells for treating cancer and other diseases,” Dr. Sun says. in the Proceedings of the National Academy of Sciences. 

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