Ohio — Researchers have taken the next step in confirming the identity of
previously unknown gene mutation that drives lung cancer development. Scientists
at The Ohio State University Comprehensive Cancer Center – Arthur G. James
Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)
originally identified the mutation in one patient out of nine with advanced
lung cancer who responded well to the drug sorafenib. The clinical trial involved
306 participants total.
two months of beginning treatment, the patient had demonstrated a near complete
response, and she remained progression-free and asymptomatic for five years
while continuing to take sorafenib by mouth.
Araujo, MD, presented these new findings Monday, June 2, 2014, at the American
Society of Clinical Oncology’s annual meeting.
this new study, the OSUCCC – James investigators have taken the next step to
learn the cancer-causing potential and mechanism of action for the mutation.
The mutation, called S214C, is located in a gene called ARAF (pronounced
A-RAF). Its discovery was reported in April 2014 issue of the Journal
of Clinical Investigation.
new study reveals that the mutation has the characteristics of “driver
mutations,” mutations whose mechanism of action directly contributes to cancer
development. Driver genes are important to identify because therapies that
target them are often particularly effective.
study showed that ARAF S214C has features characteristic of driver-gene
activity. Its specific mechanism of action explained why the patient responded
well to the drug sorafenib, which is a RAF inhibitor.
the study suggests that the mutation represents a new target for personalized
therapy in certain cases of advanced lung cancer.
recurrent but rare mutations underlie cancer growth and responsiveness, they
are not likely to be statistically called out as a potential driver of cancer
through a genome scan of several hundred or even thousands of cases because
they are so rare,” says David
Carbone, MD, director of The OSUCCC-James Thoracic
Oncology Program. “But for the patients who do have these specific genetic
mutations, having this information is critical.
“Our study suggests that we can discover
important new gene mutations that drive cancer development and progression by
analyzing genes in cancer cells from patients who fare far better or far worse
than others in a particular clinical trial.”
adds that using genome sequencing to identifying genetic mutations in a
patient’s cancer cells, as in this study, can help better match patients with
drugs that are most likely to eradicate their cancer.
which mutations are present in lung tumors can help us tailor a patient’s
treatment to the unique genetic features present in his or her cancer cells. That
knowledge can also help us develop new drugs that target previously
unrecognized gene mutations in lung and other cancers. This is a great example
of new scientific discoveries being made from clinical observations in
patients, which can then be brought back to the clinic to help future
Amann, PhD, of The OSUCCC-James was a collaborator on the current research
study. Other collaborators include Marcin Imielinski, MD, PhD and Heidi
Greulich, PhD, of Harvard Medical School and Dana Farber Cancer Institute, and
Matthew Meyerson, MD, PhD, founder and equity holder of Foundation Medicine, a
for-profit company that provides next generation sequencing diagnostic services
used in this study.
The Ohio State University
Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J.
Solove Research Institute strives to create a cancer-free world
by integrating scientific research with excellence in education and
patient-centered care, a strategy that leads to better methods of prevention,
detection and treatment. Ohio State is one of only 41 National Cancer Institute
(NCI)-designated Comprehensive Cancer Centers and one of only four centers
funded by the NCI to conduct both phase I and phase II clinical trials. The NCI
recently rated Ohio State’s cancer program as “exceptional,” the highest rating
given by NCI survey teams. As the cancer program’s 228-bed adult patient-care
component, The James is a “Top Hospital” as named by the Leapfrog Group and one
of the top cancer hospitals in the nation as ranked by U.S.News & World Report.
Media Contact: Amanda J. Harper,
OSUCCC-James Director of Media Relations, 614-685-5420 (direct), 614-293-3737
(central line) or Amanda.Harper2@osumc.edu.