Research Report: New Treatments for Melanoma

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by Richard Saltus

As recently as five years ago, progress in treating life-threatening malignant melanoma was slow. Since then, several molecularly targeted drugs have burst on the scene, and new strategies for awakening the immune system to attack the cancer cells have yielded dramatic long-term survival benefits for some patients.

“The outlook for patients has never been so good – and we anticipate that in the next year or two it will be much better,” says Louise M. Perkins, PhD, chief science officer for the Melanoma Research Alliance, which funds research on the skin cancer.

In recent years scientists have tried cancer “vaccines” that stimulate a melanoma patient’s immune system to recognize the cancer cells as foreign and send T cells to attack them. These efforts had limited success, and researchers have turned to a new strategy – inhibiting the inhibitor. Instead of stirring up the cell-killing forces, the scientists would make antibodies that would block other molecules in the immune system that restrain or turn off an immune response to prevent an over-reaction.

Dr Stephen Hodi, director of the Melanoma Center at Dana-Farber Cancer Institute

Dr Stephen Hodi, director of the Melanoma Center at Dana-Farber Cancer Institute

One such antibody is called ipilimumab, approved by the Food and Drug Administration for treating advanced melanoma in 2011. Ipilimumab disables a molecular inhibitor called CTLA-4, which normally dampens the T cell immune response. With CTLA-4 inhibitory signal blocked, T cells can continue to attack and kill melanoma cells. Last September, F. Stephen Hodi, MD, director of the Melanoma Treatment Center at  Dana-Farber reported that about 20 percent of metastatic melanoma patients treated in research studies with ipilimumab were living as long as 10 years – a stunning result.

An even newer type of antibody, which evolved from years of research that began in the laboratory of Dana-Farber’s Gordon Freeman, PhD, and is exemplified by nivolumab, blocks the interaction between a molecule called PD-1 on immune T cells and another molecule, PD-L1, that melanoma cells often have on their surface. PD-L1 helps melanoma cells evade detection and attack by the immune system. In clinical trials, many patients who were given nivolumab to target PD-1 had their tumors shrink and achieved long-term responses. While more studies are needed, nivolumab may prove more effective than ipilimumab.

Even better results may come when these immunotherapies are combined with the new drugs that target BRAF, a common mutation in melanoma cells. Alexander Eggermont, a melanoma expert from the Netherlands, told a meeting in Boston recently, “Within the next five years, 50 percent of patients with metastatic melanoma may be ‘clinically cured’.”  By that, he means the therapies will maintain long-term control of the disease, even if it is not totally eliminated.

As exciting as the new wave of treatments is, prevention is the most effective means of combating melanoma. Public education focuses on avoiding excess ultraviolet exposure from the sun and artificial sources such as tanning beds. Monthly skin self-exams and awareness of the warning signs of melanoma may be helpful in finding most melanomas when they are at an early, curable stage.

5 Comments:

  1. This is real encouraging news! My brother is one of the patients on this trial and we are hopeful that he will be one of the people that will be “clinically cured.” So thankful that he and many others have a place like Dana-Farber to go to.

  2. I was fighting against a stage IV cancer and i won, lucky my husband who helped me all the time.I think it is very important that family support to win, because i was very weak;really helped me participate in one group of victims of cancer, so my mood improved, also helped me a adviser of advisercancer-diseases.com(they are doctors).I recomended not surrender, because sometimes the first treatment does not work as me, and change doctors if it is necessary.Read positive thinking books gave me more energy.During my cancer,i changed my diet,now i eat vegetarian organic food(now i not eat meat).I think is a set of things that help me.
    Xoxo
    Wendy

  3. While positive data/results are encouraging, counting your chickens before they are hatched is misleading and risky, especially where melanoma cancer research is concerned. In honor of the many people who are not helped by current treatments, please keep working diligently and with the best collaborative efforts arounsd the world to find new and improved ways to treat this group of deadly diseases.

  4. PD-1 is not what it is expressed in the tumor cells, but rather its ligand PD-L1. PD1 is expressed in T cells. Anti-PD-1 antibodies block the interaction between PD-1 in the T-cell and PD-L1 in the tumor cells. Please correct the article and be accurate.

  5. Javier:
    Thanks for pointing this out. We’ve amended the post above.
    –Michael

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