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Genetic Testing for Melanoma

Personalized medicine is rapidly changing the cancer treatment scene

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An emphasis on personalized medicine through genetic screening can help customize treatments for patients with melanoma. Depending on the genetic profile of the patients receiving anti-cancer drugs, the outcome can vary greatly in both efficacy and onset of side effects.

Researchers at the University of Pittsburgh Cancer Institute (UPCI), a partner with UPMC CancerCenter, are working diligently to uncover the genetic key to customized treatments for melanoma. One of the researchers' most recent trials, funded by the National Institutes of Health (NIH), showed that the cancer immune therapy drug ipilimumab appears most likely to prevent recurrence in patients whose cancer shows high expression of immune-related genes.

Ipilimumab, a monoclonal antibody developed by Bristol-Myers Squibb, activates the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

"Genetic testing in this study was meant to investigate the tumor microenvironment for biomarkers of potential therapeutic predictive value," explained Ahmad A. Tarhini, MD, PhD, the study's lead investigator and associate professor of medicine and translational science, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute.

The researchers aimed to discover biomarkers that may ultimately predict which patients are more (or most) likely to benefit from a certain therapeutic agent and who should be spared the unwanted drug toxicities because of a low likelihood of clinical benefit.

"Our data is preliminary and requires additional testing and validation in larger studies," Tarhini said. "However, we believe we're on the right track towards a more personalized approach to cancer immunotherapy."

Study Specifics
Tarhini and fellow UPCI investigators Yan Lin, PhD, Hui-Min Lin, MS, Cindy Sander, BS, William A. La Framboise, PhD, and John M. Kirkwood, MD, tested the hypothesis that molecular characterization of the tumor microenvironment through gene expression profiling may generate biomarkers of therapeutic predictive value in relation to clinical benefit from ipilimumab in patients with locally/regionally advanced melanoma.

In the study, Dr. Tarhini and his colleagues ran genetic tests on obtained tumor biopsies both before and after ipilimumab treatment. The tumors were drawn from 32 patients with advanced, stage 3 melanoma who were treated by UPMC. Tarhini acknowledged that access to tumor tissue during genetic testing could pose a challenge in some patients.

All patients received standard-of-care surgery, including complete surgical removal of an advanced tumor. The investigators discovered patients had a significantly lower risk of cancer recurrence after surgery when their tumors revealed higher levels of expression of a group of immune-related genes, either before or soon after treatment with ipilimumab.

According to Tarhini, gene expression profiling identified molecular pathways and genes related to inflammation and autoimmunity that are significantly associated with clinical benefit from ipilimumab at baseline (before ipilimumab) and early on-treatment (after initiation of ipilimumab).

"A tumor microenvironment 'immune-related' gene expression signature was found to be significantly associated with ipilimumab therapeutic benefit in this patient population," Tarhini observed.

Personalized Medicine is on the Rise
"Personalized medicine as a field is generating a revolution in cancer patient care," Tarhini said. "The fact that we can better target therapeutic agents towards specific patient populations is having a major impact on the care of our patients and the overall economic cost of cancer therapy."

This field will continue to grow at a rapid pace, Tarhini told ADVANCE. "We've reached a point in the treatment of melanoma -- and cancer in general -- where we're making major improvements in the outcomes of patients through personalized medicine," he observed.

Tarhini and his fellow investigators have turned their attention to identifying biomarkers that may predict the risk of developing certain serious side effects in patients treated with the new generation of cancer immunotherapy. The team aims to develop "biomarker signatures" to help physicians customize melanoma treatment plans.

"Anti-cancer therapy can be associated with significant side effects and economic costs," Tarhini said. "Therefore, we have a major interest in the development of tests that may allow us to predict which treatment regimen is most likely to help certain patients, while sparing others the unwanted side effects and cost of medications that are unlikely to work."

The team recently reported preliminary findings on a test that may predict the risk of developing diarrhea and colitis in melanoma patients treated with ipilimumab at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. "We live in exciting times in anti-cancer therapy that are destined, in a matter of a few years, to finally create a huge and meaningful impact on cancer patient care," Tarhini observed. "We are grateful to our patients and their families whose volunteering and efforts have made such advances possible. We are also thankful to the NIH and the industry for providing us with needed resources to allow us to carry on our cancer research work."

Rebecca Mayer Knutsen is on staff at ADVANCE. Contact: rknutsen@advanceweb.com




     

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