Facebook Pixel

Can Melanoma Be Treated Without Drug Resistance?

 
Rate This
can drug resistance be avoided for melanoma? OnFocusMedia/PhotoSpin

Researchers are one step closer to understanding the growth process of melanoma skin cancer. This also brings them closer to solving a complex problem commonly associated with treating the deadliest form of skin cancer: drug resistance.

Melanoma is an aggressive form of skin cancer that starts in melanocytes which are skin cells that make the pigment melanin. They are the cells responsible for a person’s skin color, their ability to tan or freckle, and the color of their hair and eyes.

Research shows that about 40 percent of advanced melanoma tumor growth is fueled by BRAF gene mutations. The BRAF gene belongs to a class of genes known as oncogenes. When mutated — prolonged UV sun exposure and tanning beds are primary triggers — oncogenes have the potential to cause normal cells to become cancerous.

Today, more people are diagnosed with this dangerous form of skin than ever before. From 1975 to 2010, new melanoma cancer cases have steadily climbed each year from 8 cases per 100,000 men and women per year, to nearly 21.1 cases per 100,000. In 2013, an estimated 76,690 new melanomas cases were diagnosed, some in people as early as their 20s.

The 5-year survival rate for melanoma is improving, even as the number of new cases increase. This higher survival rate is largely due to new drugs called BRAF inhibitors. These treatments have shown unprecedented responses in rapidly shrinking melanoma tumors.

However, these BRAF-mutated tumors frequently show early resistance to treatment and respond only partially to BRAF inhibitors, leaving behind cancer cells that eventually lead to tumor regrowth.

Dr. Roger Lo, an associate professor and director of the melanoma clinic in dermatology at UCLA’s Jonsson Comprehensive Cancer Center (JCCC) led an international collaboration of translational research-physicians in two back-to-back studies that provide critical insights into key areas of how tumors resist BRAF inhibitor drugs.

The studies, published in the January 2014 issue of the journal Cancer Discovery, used patient biopsy samples to show the key cell-signaling pathways used by BRAF-mutant melanoma cells in learning to become resistant to inhibitor drugs.

The samples also showed how limiting BRAF inhibitors to one type allows melanoma cells to evolve and develop drug resistance.

Dr. Lo said that better understanding tumor resistance mechanisms should allow doctors to combine inhibitor drugs that block multiple resistance routes. This can prolong tumor shrinkage or make them disappear completely.

“This study lays a foundation for clinical trials to investigate the mechanisms of tumor progression in these melanoma patients,” he said in an email.

He acknowledged that three patients have already been enrolled for an ongoing clinical trial currently in the dose-finding phase.

In the second study, researchers found that as soon as BRAF inhibitor drugs are introduced, melanoma tumors are able to quickly turn on drug resistance pathways, a process called early adaptive resistance.

Over time, these pathways are further reinforced, allowing the tumor cells to break free of the BRAF inhibitor and resume growth. So while early and late resistance processes are linked, the research shows, the endgames can be quite similar although the mechanisms to these ends may differ.

Professor of medicine Dr. Antoni Ribas, a JCCC member and co-investigator in these articles said in a UCLA press release that locating the central melanoma escape pathways is an important conceptual advance to fighting BRAF inhibitor resistance.

“We now have a landscape view of how melanoma first adapts and then finds ways to overcome what is initially a very effective treatment. We have already incorporated this knowledge to the testing of new combination treatments in patients to get us ahead of melanoma and not allow it to escape,” Ribas said.

Lynette Summerill is an award-winning writer and watersport junkie who lives in San Diego with her husband and two beach loving dogs. In addition to writing about cancer-related issues for EmpowHER, her work has been seen in publications internationally.

Add a CommentComments

There are no comments yet. Be the first one and get the conversation started!

Image CAPTCHA
Enter the characters shown in the image.
By submitting this form, you agree to EmpowHER's terms of service and privacy policy

We value and respect our HERWriters' experiences, but everyone is different. Many of our writers are speaking from personal experience, and what's worked for them may not work for you. Their articles are not a substitute for medical advice, although we hope you can gain knowledge from their insight.

Metastatic Melanoma

Get Email Updates

Related Topics

Health Newsletter

Receive the latest and greatest in women's health and wellness from EmpowHER - for free!