Researchers find cause of chemotherapy resistance in melanoma

September 17, 2012

Researchers with UC Irvine's Chao Family Comprehensive Cancer Center have identified a major reason why melanoma is largely resistant to chemotherapy.

UCI dermatologist Dr. Anand Ganesan and colleagues found a in melanoma cells that inhibits the cellular mechanism for detecting DNA damage wrought by chemotherapy, thereby building up tolerance to cancer-killing drugs.

Targeting this pathway, comprising the genes RhoJ and , heralds a new approach to treating the deadly skin cancer, which claims nearly 10,000 U.S. lives each year. Study results appear online in Cancer Research, a journal of the American Association for Cancer Research.

"If we can find a way to turn off the pathway responsible for this resistance, melanoma tumors would suddenly become sensitive to therapies we've been using for the last 20 years," said Ganesan, assistant professor of dermatology and at UCI.

In pursuit of a cause for the chemo tolerance, he and his colleagues performed a genome-wide scan for genes controlling drug resistance in melanoma cells. Their search identified RhoJ, a gene normally involved in . They saw that in response to drug-induced DNA damage in a melanoma cell, RhoJ activated another gene, Pak1, which initiated a molecular cascade suppressing the cell's ability to sense this damage – and blocking the apoptosis process.

"Normally, such drug-induced DNA damage would result in cell death," Ganesan said. "But this blunting of allows to mutate and proliferate. Being capable of rapid adaptation and change is a hallmark feature of this challenging form of cancer and makes it very difficult to treat."

On the heels of this discovery, he and colleagues have begun exploring methods to inhibit the genes responsible for this DNA damage tolerance. What they come up with could one day supplement chemotherapy treatments for melanoma, Ganesan added.

Explore further: Genetics of melanoma chemoresistance

More information: cancerres.aacrjournals.org/con … CAN-12-0775.abstract

Related Stories

Genetics of melanoma chemoresistance

June 6, 2011
Malignant melanoma is a highly aggressive and notoriously chemoresistant form of cancer. In a new paper, Ohanna et al. reveal that anti-melanoma drugs may, paradoxically, induce a senescence-associated secretory profile ("secretome") ...

Study identifies human melanoma stem cells

August 23, 2012
(Medical Xpress)—Cancer stem cells are defined by three abilities: differentiation, self-renewal and their ability to seed a tumor. These stem cells resist chemotherapy and many researchers posit their role in relapse. ...

Scientists find molecule in immune system that could help treat dangerous skin cancer

July 8, 2012
Researchers from Brigham and Women's Hospital (BWH) have made a groundbreaking discovery that will shape the future of melanoma therapy. The team, led by Thomas S. Kupper, MD, chair of the BWH Department of Dermatology, and ...

Researchers find potential solution to melanoma's resistance to vemurafenib

February 28, 2012
Researchers at Moffitt Cancer Center in Tampa, Fla., and colleagues in California have found that the XL888 inhibitor can prevent resistance to the chemotherapy drug vemurafenib, commonly used for treating patients with melanoma.

Molecule's role in cancer suggests new combination therapy

March 1, 2012
Researchers at the University of Illinois at Chicago College of Medicine have found that a molecule found at elevated levels in cancer cells seems to protect them from the "cell-suicide" that is usually triggered by chemotherapy ...

Recommended for you

New bowel cancer drug target discovered

October 17, 2017
Researchers at the Francis Crick Institute have discovered a new drug target for bowel cancer that is specific to tumour cells and therefore less toxic than conventional therapies.

Using artificial intelligence to improve early breast cancer detection

October 17, 2017
Every year 40,000 women die from breast cancer in the U.S. alone. When cancers are found early, they can often be cured. Mammograms are the best test available, but they're still imperfect and often result in false positive ...

Many pelvic tumors in women may have common origin—fallopian tubes

October 17, 2017
Most—and possibly all—ovarian cancers start, not in ovaries, but instead in the fallopian tubes attached to them.

Researchers find novel mechanism of resistance to anti-cancer drugs

October 17, 2017
The targeted anti-cancer therapies cetuximab and panitumumab are mainstays of treatment for advanced colorectal cancer, the second leading cause of cancer-related deaths in the United States. However, many patients have tumors ...

New assay may boost targeted treatment of non-Hodgkin lymphoma

October 17, 2017
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer and the most frequently diagnosed non-Hodgkin lymphoma worldwide (nearly 40% of cases). Recent advancements indicate that both the prognosis and choice of treatment ...

Biology of childhood brain tumor subtypes offers clues to precision treatments

October 17, 2017
Researchers investigating pediatric low-grade gliomas (PLGG), the most common type of brain tumor in children, have discovered key biological differences in how mutated genes combine with other genes to drive this childhood ...

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.