Mutations in the BRAF gene predict sensitivity to a novel class of cancer drugs

November 06, 2005

NEW YORK, November 6, 2005 - A team of researchers led by scientists at Memorial Sloan-Kettering Cancer Center have discovered that a new class of drugs -- now in early stage clinical trials -- work best in patients with mutations in the BRAF gene. BRAF is a protein that plays a central role in the growth and survival of cancer cells and is mutated in the majority of patients with melanoma and in a minority of patients with colon, breast, and lung cancers. The findings, available in an advance online publication of Nature, represent a potential targeted therapy tailored for patients whose tumors contain this mutation.

The researchers found that drugs that inhibit a protein called MEK selectively inhibited the growth of cancer cells lines and tumors that have a mutated BRAF gene. One of these drugs, PD0325901 (developed by Pfizer Research and Development), is now being tested in clinical trials of patients with melanoma, colon, breast, and lung cancers. In addition, by re-analyzing the data on more than 42,000 compounds tested by the National Cancer Institute against a panel of 60 cancer cell lines, the investigators were able to identify a small number of other compounds that also selectively inhibit tumors that have the BRAF mutation. While the mechanism of action of some of these compounds has yet to be determined, several of the most effective compounds were also inhibitors of the MEK protein.

"We find that all tumors with the BRAF mutation and some with the RAS mutation are sensitive to drugs that inhibit MEK," explained Dr. Neal Rosen, Professor of Medicine and a member and laboratory head in the Molecular Pharmacology and Chemistry Program at Memorial Sloan-Kettering and the study's senior author. "Translating these findings into a strategy for treating patients whose tumors are dependent upon this specific genetic change is the next step, and such clinical trials are now ongoing."

"The BRAF mutation was first identified by a consortium of investigators searching for proteins that are frequently mutated in human cancer," said Dr. David Solit, the study's first author and a medical oncologist at Memorial Sloan-Kettering who is also a member of Dr. Rosen's laboratory. This project, an outgrowth of the Human Genome Project, called the Cancer Genome Project, has the goal of identifying the causative mutations that cause human cancers.

"This represents what we believe will be the first of a series of new drugs that specifically target cancer cells that contain mutations identified by the Cancer Genome sequencing effort," said Dr. Solit. "The hope is that these new targeted therapies will be more effective and less toxic than traditional chemotherapies."

The study's other researchers were Christine A. Pratilas, Ayana Sawai, Andrea Basso, Qing Ye, Jose M. Lobo, and Yuhong She, all of Memorial Sloan-Kettering; Drs. Levi A.Galloway, Gad Getz, Todd R. Golub, and William R. Sellers of Dana-Farber Cancer Institute and Broad Institute of MIT and Harvard; Dr. Iman Osman of New York University Medical College; and Dr. Judith Sebolt-Leopold of Pfizer Global Research and Development.
-end-
This work was supported by grants from the National Institutes of Health, the William H. Goodwin and Alice Goodwin Foundation for Cancer Research, the Memorial Sloan-Kettering Cancer Center Experimental Therapeutics Center, the Waxman Foundation, the Howard Hughes Medical Institute, Golfers Against Cancer, and the American Society of Clinical Oncology.

Memorial Sloan-Kettering Cancer Center is the world's oldest and largest institution devoted to prevention, patient care, research, and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose, and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide. For more information, go to www.mskcc.org

Memorial Sloan Kettering Cancer Center

Related Cancer Cells Articles from Brightsurf:

Cancer researchers train white blood cells to attacks tumor cells
Scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and Dresden University Medicine, together with an international team of researchers, were able to demonstrate that certain white blood cells, so-called neutrophil granulocytes, can potentially - after completing a special training program -- be utilized for the treatment of tumors.

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.

Breast cancer cells use message-carrying vesicles to send oncogenic stimuli to normal cells
According to a Wistar study, breast cancer cells starved for oxygen send out messages that induce oncogenic changes in surrounding normal epithelial cells.

Breast cancer cells turn killer immune cells into allies
Researchers at Johns Hopkins University School of Medicine have discovered that breast cancer cells can alter the function of immune cells known as Natural killer (NK) cells so that instead of killing the cancer cells, they facilitate their spread to other parts of the body.

Breast cancer cells can reprogram immune cells to assist in metastasis
Johns Hopkins Kimmel Cancer Center investigators report they have uncovered a new mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body.

Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.

Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.

First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.

Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.

Read More: Cancer Cells News and Cancer Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.