How Melanoma Skin Cancer Can Resist Chemotherapy is
Study results suggest new approach to treating most
deadly skin cancer
Melanoma patient after cancer
surgically removed from head... currently must successful
Sept. 17, 2012 – Melanoma – the deadly skin cancer,
major killer of seniors and most rapidly increasing cancer – has been
almost unstoppable and a major reason has been its resistance to
chemotherapy. This advantage may be coming to an end with the discovery
of a genetic pathway in melanoma cells that blocks the cellular
mechanism for detecting DNA damage wrought by chemotherapy, thereby
building up tolerance to cancer-killing drugs.
Dr. Anand Ganesan,
dermatologist, and colleagues UC Irvine’s Chao Family Comprehensive
Cancer Center have identified this as a major reason why melanoma is
largely resistant to chemotherapy.
Targeting this pathway, comprising the genes RhoJ
and Pak1, 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
“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 biological chemistry at
This announcement just follows by a few days the
news that researchers claimed discovery of a novel opportunity for
melanoma skin cancer diagnostics, treatment and prevention. Yujiang Geno Shi, PhD, from
Brigham and Women's Hospital,
Department of Medicine, and George F. Murphy, MD, from BWH's Department
of Pathology made the discovery.
"Dr. Shi and colleagues have discovered an exciting
new connection between the loss of a specific chemical mark in the
genome and the development of melanoma," said Anthony Carter, PhD, of
the National Institutes of Health's National Institute of General
Medical Sciences, which mainly funded the research.
In pursuit of a cause for the chemo tolerance,
UCI colleagues performed a genome-wide scan for genes controlling
drug resistance in melanoma cells. Their search identified RhoJ, a gene
normally involved in blood vessel growth. 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 DNA damage
response allows melanoma cells 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.
Hsiang Ho, Jayavani Aruri, Rubina Kapadia and
Hootan Mehr of UCI and Michael A. White of the University of Texas
Southwestern Medical Center at Dallas participated in the study, which
received support from the National Institutes of Health, the University
of California Cancer Research Coordinating Committee, the American
Cancer Society, Outrun the Sun Inc. and the Robert A. Welch Foundation.
About the University of California, Irvine: Founded
in 1965, UCI is a top-ranked university dedicated to research,
scholarship and community service. Led by Chancellor Michael Drake since
2005, UCI is among the most dynamic campuses in the University of
California system, with nearly 28,000 undergraduate and graduate
students, 1,100 faculty and 9,000 staff. Orange County’s second-largest
employer, UCI contributes an annual economic impact of $4 billion. For
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Links to More Archived Stories on Melanoma
Melanoma is a form of cancer that
begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other
pigmented tissues, such as in the eye or in the intestines.
It is estimated that 76,250 men and women (44,250 men and 32,000 women) will be diagnosed with and 9,180 men
and women will die of melanoma of the skin in 2012.
From 2005-2009, the median age at diagnosis for melanoma of the skin was 61 years of age.
Approximately 0.6% were diagnosed under age 20; 6.8% between 20 and 34; 10.7% between 35 and 44; 18.2%
between 45 and 54; 21.6% between 55 and 64; 18.8% between 65 and 74; 16.7% between 75 and 84; and 6.6% 85+ years of age.
The age-adjusted incidence rate was 21.0 per 100,000 men and women per year.
From 2005-2009, the median age at death for melanoma of the skin was 68 years of age. Approximately 0.1% died
under age 20; 2.6% between 20 and 34; 5.6% between 35 and 44; 13.5% between 45 and 54; 19.9% between 55 and 64; 21.2% between 65
and 74; 24.1% between 75 and 84; and 12.9% 85+ years of age.
The age-adjusted death rate was 2.7 per 100,000 men and women per year. These rates are based on patients who
died in 2005-2009 in the US.
Based on rates from 2007-2009, 1.99% of men and women born today will be diagnosed with melanoma of the skin
at some time during their lifetime. This number can also be expressed as 1 in 50 men and women will be diagnosed with melanoma of
the skin during their lifetime. These statistics are called the
lifetime risk of developing cancer.
Sometimes it is more useful to look at the
probability of developing melanoma of the skin between two age groups. For example,
0.99% of men will develop melanoma of the skin between their 50th and 70th birthdays compared to 0.60% for women
On January 1, 2009, in the United States there were approximately 876,344 men and women alive who had a
history of melanoma of the skin - 427,810 men and 448,534 women.
Couples encouraged to examine each other for
suspicious moles that could be skin cancer. Researchers estimate that 40
– 50% of people in the U.S. who live to age 65 will have nonmelanoma
skin cancer at least once.