Combined BRAF-targeted and immunotherapy shows promise for melanoma treatment

June 15, 2010

Combined targeted therapy against the BRAF/MAPK pathway with immunotherapy shows promise as a new therapeutic approach for the treatment of melanoma, according to results of a preclinical study published in Cancer Research, a journal of the American Association for Cancer Research.

"Our results provide preclinical evidence for the rational combination of BRAF-targeted therapy and in the treatment of this most dangerous type of ," said lead researcher Jennifer A. Wargo, M.D., division of surgical oncology at Massachusetts General Hospital, Boston.

"By blocking the oncogenic BRAF, tumor antigen expression may be restored. This would make the tumors susceptible to strategies incorporating immunotherapy," she said.

Previous studies have shown that melanoma treatment with selective BRAF inhibitors are very effective and result in a high initial response rate, but the response is temporary. An alternative approach would be to combine other agents and extend the duration of treatment response.

Using biopsies of melanoma tumors, the researchers investigated the effects of mitogen-activated (MAPK) pathway inhibition vs. selective inhibition of BRAF-V600E on T-cell function.

Inhibition of the MAPK pathway with a specific inhibitor of BRAF-V600E resulted in increased expression of antigens, which was associated with improved recognition by antigen-specific T-cell. T-cell function was not compromised after treatment with BRAF-V600E.

Mario Colombo, Ph.D., director of molecular immunology at the Italian National Cancer Institute and senior editor for Cancer Research, said these results advance cancer research by offering new arguments to sustain the combination of selective targeted therapy with immunotherapy.

"This study shows the need for considering the effect of off-targeted drug therapy on the many aspects of host immune response to make real the combination of chemo- and immunotherapy," Colombo said. "It also prompts the idea of performing vaccination in the attempt to eradicate the disease and prevent recurrence."

Several clinical trials are underway using agents that selectively inhibit BRAF-V600E in patients with metastatic melanoma. These studies have shown impressive response rates, though durability of response remains an issue, according to Wargo.

Results of this study provide a basis for combining this type of therapy with immunotherapy, with the goal of improving durability of responses.

Related Stories

Recommended for you

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

A metabolic treatment for pancreatic cancer?

August 15, 2017
Pancreatic cancer is now the third leading cause of cancer mortality. Its incidence is increasing in parallel with the population increase in obesity, and its five-year survival rate still hovers at just 8 to 9 percent. Research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.