General Health

General health issues, Medical conditions, Research and studies and more

Mental Health

Natural Medicine

Nutritional supplements, Herbs, Alternative medicine and more…

Wellness & Lifestyle

Nutrition, Diets, Healthy living, Detox, Exercise and Physical Fitness, Sports Fitness and more…

Women’s Health

Relationships, Pregnancy, Birth control, Menopause and more

Home » Information, News

Protein Block

Article / Review by on November 6, 2013 – 11:11 pmNo Comments

Protein Block
Genetic error in some lung cancers may offer target for therapies

A fine-grained scan of DNA in lung cancer cells has revealed a gene fusion—a forced merger of two normally separate genes—that spurs the cells to divide rapidly, scientists at Harvard Medical School, Dana-Farber Cancer Institute and the University of Colorado report in a new paper in the journal Nature Medicine. Treating the cells with a compound that blocks a protein encoded by one of those genes—NTRK1—caused the cells to die.

Pasi A. Jänne. Image: Sam Ogden/Dana-Farber
Pasi A. Jänne. Image: Sam Ogden/Dana-Farber

The finding suggests that the fusion ofNTRK1 to other genes fuels the growth of some lung adenocarcinomas (a form of non-small cell lung cancer), and that drugs that target NTRK1’s protein product could be effective in patients whose lung tumors harbor such fusions.

“Treatment with targeted therapies is now superior to standard chemotherapy for many patients with lung cancers that harbor genetic changes, including those with fusions involving the gene ALK,” said Pasi A. Jänne, HMS associate professor of medicine at Brigham and Women’s Hospital and Dana-Farber, and senior co-author of the paper. “We know of several other genes that are fused in lung cancer and that offer attractive targets for new therapies. Our discovery places lung adenocarcinomas with NTRK1 fusions squarely within that group.”

In the study, researchers performed next-generation DNA sequencing tests, which read the individual elements of the genetic code over long stretches of chromosomes, on tumor samples from 36 patients with lung adenocarcinomas whose tumors did not contain any previously known genetic alterations that could be found with standard clinical tests. In two of those samples—both from women who had never smoked—investigators found that a key region of the NTRK1 gene had become fused to normally distant genes (to the gene MPRIP in one patient; and the gene CD74 in the other).

NTRK1 holds the blueprint for a protein called TRKA, which dangles from the surface of cells and receives growth signals from other cells. The binding of NTRK1 to other genes causes TRKA to issue cell-growth orders on its own, without being prompted by outside signals.

In the laboratory, investigators mixed NTRK1-inhibiting agents into lung adenocarcinoma cells harboring NTRK1 fusions. The result was a dampening of TRKA’s activity and the death of the cancer cells.

Investigators then designed a new test using fluorescence in situ hybridization (FISH) to detect NTRK1 fusions and tested an additional 56 tumor samples. In total, 3 of 91 tumor samples that had no other sign of cancer-causing genetic abnormalities had fusions involving NTRK1.

“These findings suggest that in a few percent of lung adenocarcinoma patients—in whose cancer cells we had previously been able to find no genetic abnormality—tumor growth is driven by a fusion involving NTRK1,” Jänne said. “Given that lung cancer is a common cancer, even a few percent is significant and translates into a large number of patients. Our findings suggest that targeted therapies may be effective for this subset of lung cancer patients.”

“This is still preclinical work,” said Robert Doebele of the University of Colorado Cancer Center and co-author on the paper, “but it’s the first—and maybe even second and third—important step toward picking off another subset of lung cancer with a treatment targeted to the disease’s specific genetic weaknesses.”

The research was supported by the Colorado Bioscience Discovery Evaluation Grant Program, the National Institutes of Health, and the Boettcher Foundation’s Webb-Waring Biomedical Research Program, the Cammarata Family Foundation Research Fund, and the Nirenberg Fellowship at Dana-Farber.

###

About Harvard Medical School (HMS)

Driving Change. Building Momentum. Making History.

“Since 1872, Harvard Medical School has been the incubator of bold ideas—a place where extraordinary people advance education, science and health care with unrelenting passion.

Whether training tomorrow’s doctors and scientists, decoding the fundamental nature of life, advancing patient care or improving health delivery systems around the world, we are never at rest. Allied with some of the world’s best hospitals, research institutes and a University synonymous with excellence, the School’s mission remains as ambitious as it is honorable: to alleviate human suffering caused by disease.”

More at Harvard Medical School & Harvard Medical School. Generations of Leaders.

Harvard Medical School. Medicinezine.com Harvard Medical School (HMS) logo

_________________________________________________

###

About Harvard School of Public Health (HSPH)

Harvard School of Public Health is dedicated to advancing the public’s health through learning, discovery and communication. More than 400 faculty members are engaged in teaching and training the 1,000-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children’s health to quality of care measurement; from health care management to international health and human rights.

More at Harvard School of Public Health (HSPH) & Harvard School of Public Health (HSPH). History.

Medicinezine.com Harvard School of Public Health (HSPH) Logo 540 ok

_________________________________________________

###

About Harvard University.

Established in 1636, Harvard is the oldest institution of higher education in the United States. The University, which is based in Cambridge and Boston, Massachusetts, has an enrollment of over 20,000 degree candidates, including undergraduate, graduate, and professional students. Harvard has more than 360,000 alumni around the world.

Harvard University is devoted to excellence in teaching, learning, and research, and to developing leaders in many disciplines who make a difference globally. Harvard faculty are engaged with teaching and research to push the boundaries of human knowledge. For students who are excited to investigate the biggest issues of the 21st century, Harvard offers an unparalleled student experience and a generous financial aid program, with over $160 million awarded to more than 60% of our undergraduate students. The University has twelve degree-granting Schools in addition to the Radcliffe Institute for Advanced Study, offering a truly global education.

‘Universities nurture the hopes of the world: in solving challenges that cross borders; in unlocking and harnessing new knowledge; in building cultural and political understanding; and in modeling environments that promote dialogue and debate… The ideal and breadth of liberal education that embraces the humanities and arts as well as the social and natural sciences is at the core of Harvard’s philosophy. ’/ Drew Gilpin Faust

More About Harvard University & About Harvard University. Information.

###

* The above story is adapted from materials provided by Harvard University

_________________________________________________________________

Medicinezine.com Harvard University Logo

Tags: , , , , , , , ,

Leave a comment!

Add your comment below, or trackback from your own site. You can also subscribe to these comments via RSS.

Be nice. Keep it clean. Stay on topic. No spam.

You can use these tags:
<a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>

Notify me of followup comments via e-mail. You can also subscribe without commenting.