Solution to Melanoma’s Resistance to Drug Therapy is
Goal of Team Funded by NIH
The deadliest of skin cancers a growing problem with
increasing number of seniors
Dec. 5, 2013 - Melanoma remains the deadliest, most
aggressive form of skin cancer, primarily due to the resistance of the
advanced cancer to drug therapy, despite the new BRAF inhibitors that
show success in early treatment. And, it is a growing threat, since in
often attacks seniors, the most rapidly increasing age group. There
is new hope, however, from a $12.5 million grant by the National
Institutes of Health to a team of melanoma scientists to find a solution
to melanoma’s drug resistance.
These scientists from The Wistar Institute and the
University of Pennsylvania received this grant for a five-year program
to continue trailblazing research on targeted therapies in melanoma.
Team leader Meenhard Herlyn, D.V.M., D.Sc.,
director of Wistar's Melanoma Research Center and professor in the
Institute's Molecular and Cellular Oncogenesis Program, brought together
the team of melanoma scientists to study the intractable problem of
melanoma drug resistance.
"Inevitably, advanced melanoma becomes resistant to
drug therapy, and despite the new BRAF inhibitors that have proven very
successful during initial stages of treatment, the disease returns
stronger than before," said Herlyn.
"We can overcome this drug resistance by utilizing
a deeper understanding of melanoma biology to develop more effective
therapies or new methods of boosting the effectiveness of existing
"This grant enables scientists from different
backgrounds—tumor biology, structural biology, chemistry, pathology,
oncology, and biostatistics—to pool our talents and tackle melanoma from
different vantage points," said Herlyn.
According to Herlyn, there are three major goals of
this five-year project. First, they seek to better understand the
ultimate fate of dying melanoma cells. Cancer therapies are currently
designed to trigger apoptosis (an inherent self-destruct mechanism
within cells) or necrosis (the death of the cell outright).
However, recent data suggests that two additional
fates are common after drug therapy: autophagy (where a cell can survive
by digesting damaged portions of itself) and quiescence (a sort of
stand-by mode that allows a cell to survive by "riding out" an attack).
In particular, the researchers will look for new methods to block cells
from using autophagy or any form of hibernation to survive drug therapy.
The second goal of the program will be to generate
"second-generation" drugs, where melanoma biologists will team with
molecular biologists and chemists to develop new molecular compounds to
form the basis of new drugs that are more potent and effective
treatments than their predecessors.
The third goal is based on the notion that
melanomas are complex tumors, driven by multiple genetic anomalies. As
such, the team will develop strategies that pair multiple drugs - both
current and experimental therapies - to see which combinations are most
effective by targeting different mutations.
The project is supported by five cores, including
pathology, cell biology, biostatistics, medical chemistry and an
administrative core, which secures a strong infrastructure in support of
"This team is positioned to answer important
multidisciplinary questions regarding the biology of melanoma cells with
the ultimate goal of achieving a cure," said Herlyn. "I am excited for
this collaborative effort that will lay the groundwork for new therapies
and strategies in melanoma research."
The team includes Maureen Murphy, Ph.D., Wistar
professor and program leader of the Molecular and Cellular Oncogenesis
Program, associate director of Faculty Development, and associate
director for Education; Ronen Marmorstein, Ph.D., Wistar program leader
of the Gene Expression and Regulation Program; Jessie Villanueva, Ph.D.,
Wistar assistant professor of the Molecular and Cellular Oncogenesis
Program and member of The Wistar Institute Melanoma Research Center;
Ashani Weeraratna, Ph.D., Wistar assistant professor in the Tumor
Microenvironment and Metastasis Program and member of The Wistar
Institute Melanoma Center; Jeffrey Winkler, Ph.D., Merriam Professor of
Chemistry at the University of Pennsylvania; and Ravi K. Amaravadi,
M.D., associate professor of medicine at the Hospital of the University
Links to More Archived
Stories on Melanoma Cancer
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.
men and women (44,250 men and 32,000 women) were expected to be
diagnosed with and 9,180 men and women to die of
melanoma of the skin
the median age at diagnosis for melanoma of the skin was 61
years of age.
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.
age-adjusted incidence rate was 21.0 per 100,000 men and women
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.
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
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
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.