Study of 'super responder' reveals new oncogene for lung cancer

June 13, 2014 by Amanda J. Harper, Ohio State University Medical Center

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.

Within 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.

Luiz Araujo, MD, presented these new findings Monday, June 2, 2014, at the American Society of Clinical Oncology's annual meeting.

In this new study, the OSUCCC – James investigators have taken the next step to learn the -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.

This 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.

This 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.

Overall, the study suggests that the mutation represents a new target for personalized therapy in certain cases of advanced .

"If 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 and progression by analyzing genes in cancer cells from patients who fare far better or far worse than others in a particular clinical trial."

Carbone 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.

"Knowing 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 . That knowledge can also help us develop new drugs that target previously unrecognized gene 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 patients."

Explore further: Recurrent but rare mutations might underlie cancer growth

More information: "Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma." Marcin Imielinski, Heidi Greulich, Bethany Kaplan, Luiz Araujo, Joseph Amann, Leora Horn, Joan Schiller, Miguel A. Villalona-Calero, Matthew Meyerson, David P. Carbone Published in Volume 124, Issue 4 J Clin Invest. 2014; 124(4):1582–1586 DOI: 10.1172/JCI72763

Related Stories

Recurrent but rare mutations might underlie cancer growth

February 26, 2014
A potential new gene mutation that might drive lung cancer development and growth has been identified by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard ...

Researchers develop process to help personalize treatment for lung cancer patients

June 3, 2014
Moffitt Cancer Center researchers, in collaboration with the Lung Cancer Mutation Consortium, have developed a process to analyze mutated genes in lung adenocarcinoma to help better select personalized treatment options for ...

Next-generation genome screening is step toward precision cancer medicine for lung cancer

November 14, 2013
Precision cancer medicine has taken a strong step forward at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) with the addition ...

ALK, ROS1 and now NTRK1: Study shows prevalence of new genetic driver in lung cancer

May 31, 2014
A University of Colorado Cancer Center study presented at the 50th Annual Meeting of the American Society for Clinical Oncology (ASCO) draws a line from mutation of the gene NTRK1, to its role as an oncogene in non-small ...

Non-uniform genetic mutations identified in lung cancers could lead to targeted treatment

April 23, 2014
The research, published in the journal Oncotarget, explored tumour heterogeneity – where different cells have different appearances or their own DNA signatures within the same cancer. Such differences could make it difficult ...

Potential breast cancer drug performs well in early clinical trials

June 3, 2014
(Medical Xpress)—A drug previously studied to improve chemotherapy may be effective in treating patients with cancers related to the BRCA 1 or 2 genetic mutations, as well as patients with BRCA-like breast cancers, according ...

Recommended for you

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

New immunotherapy approach boosts body's ability to destroy cancer cells

January 12, 2018
Few cancer treatments are generating more excitement these days than immunotherapy—drugs based on the principle that the immune system can be harnessed to detect and kill cancer cells, much in the same way that it goes ...

Cancer's gene-determined 'immune landscape' dictates progression of prostate tumors

January 12, 2018
The field of immunotherapy - the harnessing of patients' own immune systems to fend off cancer - is revolutionizing cancer treatment today. However, clinical trials often show marked improvements in only small subsets of ...

FDA approves first drug for tumors tied to breast cancer genes

January 12, 2018
(HealthDay)—The U.S. Food and Drug Administration on Friday approved the first drug aimed at treating metastatic breast cancers linked to the BRCA gene mutation.

Breast cancer gene does not boost risk of death: study

January 12, 2018
Young women with the BRCA gene mutation that prompted actress Angelina Jolie's pre-emptive and much-publicised double mastectomy are not more likely to die after a breast cancer diagnosis, scientists said Friday.

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.