AURORA, Colo. (PRWEB) October 27, 2013

A study lead by scientists at University of Colorado Cancer Center and Dana-Farber Cancer Institute in Boston has uncovered a new sub-type of lung cancer. The study revealed a gene fusion - a forced merger of two normally separate genes that spurs the cells to divide rapidly causing non-small cell lung cancer. The study is published in the journal Nature Medicine.

Scientists from CU Cancer Center and Dana-Farber collaborated on the finding. The group went a step beyond identifying the gene mutation, NTRK1, that drives some lung cancers. The scientists also showed the abnormal cells can be targeted by several drugs.

Whether a drug is already is in clinical trials, or already approved for another cancer, or just sitting on the pharma shelf somewhere, many drugs exist that turn off these candidate genes," said Robert C. Doebele, MD, PhD, the studys senior author and investigator at the CU Cancer Center.

Doebele found Array BioPharma in Boulder, Colo. happened to have several compounds specific to NTRK1. The group showed that mutated NRTK1 genes in cells treated with drug candidate ARRY-470 and others was effectively turned off. The drug blocks a protein causing cancer cells to die.

This is still preclinical work," Doebele says, "but it's the first and maybe even second and third important steps toward picking off another subset of lung cancer with a treatment targeted to the disease's specific genetic weaknesses."

Foundation Medicine, Inc. 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 joining 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 TRKAs activity and the death of the cancer cells.

Leila Varella-Garcia, PhD, at CU Cancer Center then designed a new test using fluorescence in situ hybridization (FISH) to detect NTRK1 fusions and tested an additional 56 tumor samples. Three of 91 tumor samples, which had no other sign of cancer-causing genetic abnormalities, had fusions involving NTRK1.

Read the original here:
New Genetic Error in Some Lung Cancers Identified by CU Scientists

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