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

Cell-weighing method could help doctors choose cancer drugs

November 20, 2017
Doctors have many drugs available to treat multiple myeloma, a type of blood cancer. However, there is no way to predict, by genetic markers or other means, how a patient will respond to a particular drug. This can lead to ...

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

Pharmacoscopy improves therapy for relapsed blood cancer in a first clinical trial

November 16, 2017
Researchers at CeMM and the Medical University of Vienna presented a preliminary report in The Lancet Hematology on the clinical impact of an integrated ex vivo approach called pharmacoscopy. The procedures measure single-cell ...

Wider sampling of tumor tissues may guide drug choice, improve outcomes

November 15, 2017
A new study focused on describing genetic variations within a primary tumor, differences between the primary and a metastatic branch of that tumor, and additional diversity found in tumor DNA in the blood stream could help ...

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.