Melanoma and the Problem of Drug Resistance
8 October 2015 | Science
In 2002, researchers discovered a link between mutated BRAF genes and nearly half of all melanoma tumors. Since then, BRAF inhibitors—drugs that target mutated BRAF—have become a leading go-to weapon in the battle against melanoma. Their job is to cut off signals sent by altered BRAF that promote the rapid growth and division of cancer cells.
BRAF Inhibitors and Drug Resistance
Studies show that BRAF inhibitors shrink melanoma tumors faster and better than chemotherapy. Unfortunately, the treatment’s success is short lived. It only takes about six months for cancer cells to figure out how to use alternate pathways to grow and divide once again.
Eventually, melanoma tumors become resistant to the drug’s effects, rendering the treatment essentially useless. This is similar to how skin, ear and respiratory infections can build up resistance to certain overused antibiotics.
Another problem with BRAF inhibitors is that 20 percent of users go on to develop a different type of skin cancer called squamous cell carcinomas. Although this form of skin cancer isn’t as serious as melanoma, they still require removal and treatment.
Combination Treatments for Melanoma: BRAF and MEK Inhibitors
Studies show that combining BRAF inhibitors with another targeted drug, MEK inhibitors, leads to better results.
You might be most familiar with the success of combination therapies to treat AIDS. Over the past two decades, the introduction of a triple cocktail—a combination of three gene-inhibiting drugs—has changed AIDS from being a deadly disease to making it more of a chronic, manageable condition. One goal with melanoma research is to come up with a combination drug therapy that works as well on melanoma.
How are Researchers Combating Drug Resistance?
The Melanoma Research Alliance is helping to fund many of these research projects in the hopes of finding better treatment options with improved outcomes.
- Several ongoing clinical trials are exploring new drugs and drug combinations.
- Other studies are looking into whether taking medications intermittently instead of daily might lower the risk of drug resistance.
- Laboratory tests and clinical trials explore whether drug treatment should continue once cancer progresses to a certain point. Some studies suggest there may be benefits of continuing drug therapy, while other findings suggest otherwise.
Another innovative therapy now available for melanoma is immunotherapy. With this treatment, medications called immune checkpoint inhibitors stimulate the immune system to recognize and destroy cancer cells more effectively.
Studies are currently looking at the effectiveness of combining immunotherapy with other treatments, such as targeted therapies. Researchers also are exploring whether it’s best to start immunotherapy early in the treatment process or after the disease progresses.
Read more about research funded by the Melanoma Research Alliance.Some of this information was presented as part of our 7th Annual Scientific Retreat, which was held in February 2015. You can read about MRA's Scientific Retreat.
Research Targeted Therapy Immunotherapy Treatment