With over 8,000 Americans dying from the disease every year, metastatic melanoma is a form of cancer that is both dangerous and difficult to treat. Fortunately, the past decade has seen considerable improvement in the treatment of metastatic melanoma, largely due to new classes of anti-cancer drugs. One such class, called MAP Kinase inhibitors, initially work very well in over 80% of patients, but within 12 months most of these cancers will become resistant to therapy and grow back. By studying how this resistance is developed, cancer researchers hope to learn how to block the process, thereby increasing the effectiveness of therapies and saving thousands of lives. Our research group has rec...

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With over 8,000 Americans dying from the disease every year, metastatic melanoma is a form of cancer that is both dangerous and difficult to treat. Fortunately, the past decade has seen considerable improvement in the treatment of metastatic melanoma, largely due to new classes of anti-cancer drugs. One such class, called MAP Kinase inhibitors, initially work very well in over 80% of patients, but within 12 months most of these cancers will become resistant to therapy and grow back. By studying how this resistance is developed, cancer researchers hope to learn how to block the process, thereby increasing the effectiveness of therapies and saving thousands of lives. Our research group has recently discovered a new way that melanoma cells become resistant to anti-cancer therapies: By changing their shape. As these cells spread through the bodies of patients, they often cover their surfaces in small, round, bubble-shaped structures called "blebs". We discovered that these blebs help turn on the signaling proteins that rewire cellular circuitry and allow cancer cells to inappropriately multiply and survive - for this reason we named the phenomenon "bleb signaling". We found that when melanoma cells are treated with MAP Kinase inhibitors, they activate bleb signaling, using its pro-survival signaling to overcome the treatment that would otherwise kill them. When bleb signaling is blocked, these cancer cells can no longer escape the effects of the anti-cancer therapy and die. With the funding we receive from CPRIT, we will explore how this drug resistance through bleb signaling works, how bleb signaling can itself be targeted with new therapies, and whether these therapies work in patients - not just in the controlled environment of the laboratory. We hope that this work will lead to more knowledge of how cancer operates, more treatment options for doctors and patients, and ultimately, more years of life for those diagnosed with metastatic melanoma.

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