Navigation Links
NTRK1: A new oncogene and target in lung cancer

To the list of oncogenic drivers of lung cancer that includes ALK, EGFR, ROS1 and RET, results of a University of Colorado Cancer Center study presented at ASCO 2013 show that mutations in the gene NTRK1 cause a subset of lung cancers.

"We're reconceptualizing lung cancer as many, related diseases. And we need to learn to identify and treat each individually. We can treat the forms of the disease that depend on ALK and EGFR mutations. We're getting very close to treating lung cancers that depend on ROS1 and RET. And now we show another oncogenic driver of the disease that begs its own targeted treatment," says Robert C. Doebele, MD, PhD, investigator at the CU Cancer Center and assistant professor of medical oncology at the CU School of Medicine.

The group, in collaboration with Pasi A. Jnne, MD, PhD from the Dana-Farber Cancer Institute, started with lung cancer tumor samples from 36 "pan-negative" patients, meaning that no other driver oncogene had been identified. So if not EGFR, ALK and the like, what was driving the cancer? Doebele and colleagues took the question to Foundation Medicine (Cambridge, MA), which used targeted, next-gen sequencing to analyze the samples for possible mutations in a couple hundred potential oncogenes identified as drivers of other cancers. NTRK1 had been identified as a driver of thyroid cancer and so was included in the panel (though drug development had stalled due in part to the relative rarity of the thyroid disease). Sure enough, next-gen sequencing identified NTRK1 gene fusions as the potential driver in two of these samples.

Doebele and colleagues took the lead back to the CU labs, where Marileila Varella Garcia, PhD, developed a specific test for NTRK1 fusions based on fluorescence in situ hybridization (FISH), similar to what is used for ALK, ROS1 and RET fusions. This allowed the group to validate the finding of NRTK1 as a novel oncogene in these patient samples.

But the study went a step beyond identifying the oncogene. Doebele describes the relative ease with which genes that are improperly activated can be silenced "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," Doebele says.

In this case, Doebele describes "walking up the street to Array BioPharma (Boulder, CO), who happened to have several compounds specific for this gene."

The group showed that mutated NRTK1 genes in cells treated with drug candidates ARRY-772, -523, and -470 and others was effectively turned off.

"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."


Contact: Garth Sundem
University of Colorado Denver

Related medicine news :

1. New oncogene identified for breast cancer
2. Dietary glucose affects the levels of a powerful oncogene in mice
3. Hepatitis B virus promotes oncogenesis through microRNA modulation
4. Preclinical study identifies master proto-oncogene that regulates ovarian cancer metastasis
5. RET rearrangement a new oncogene and potential target in lung cancer
6. Targeted therapeutics for colon cancer to be presented at AACR meeting
7. First targeted nanomedicine to enter human clinical studies
8. SMART heart eases heart ache, targets cardiac patients emotional well-being
9. Target set on cancer gene MCL1
10. Scientists tailor cell surface targeting system to hit organelle ZIP codes
11. IBN discovers human neural stem cells with tumor targeting ability
Post Your Comments:
(Date:11/25/2015)... ... 2015 , ... Finnleo, a leader in the traditional and far-infrared sauna industry, ... far-infrared saunas. , For traditional saunas, Finnleo is offering 20% off ... and Finnleo uses only European Grade A Nordic White Spruce from sustainably grown trees. ...
(Date:11/25/2015)... ... November 26, 2015 , ... Ministers, ... Union (EU), ANDI Pan African Centres of Excellence, and public R&D institutions, civil ... for the opening of the 5th African Network for Drugs and Diagnostics Innovation, ...
(Date:11/25/2015)... FL (PRWEB) , ... November 25, 2015 , ... ... center, is encouraging people across the country to celebrate their sobriety and show ... people to post “before and after” photos this Thanksgiving with the hashtag #FacesOfGratitude ...
(Date:11/25/2015)... ... November 25, 2015 , ... The McHenry County law firm of Botto ... by Attorneys Francisco J. Botto and Alex C. Wimmer. Attorneys Botto and Wimmer represented ... IL App (2d) 130884WC. , According to court documents, Adcock testified that on May ...
(Date:11/25/2015)... ... , ... Beddit® has launched a new Android app for use ... a more intuitive SleepScore™ that rates sleep quality on a 100-point scale and makes ... by a proprietary algorithm. Beddit analyzes the data to provide an easy to understand ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... November 25, 2015 The hope ... repeated failure of IVF cycles. After failure of over ... and had lost all hopes that she would be able to conceive ever. ... child conceived after failure of over 15 IVF cycles. ... before they decided to take one last attempt with Gaudium IVF ...
(Date:11/24/2015)... 2015  Thanks to a donor with a personal ... Center,s Sister Diane Grassilli Center for Women,s Health now ... San Francisco . Fred ... with a gift of $617,320 that allowed the Center ... Tomosynthesis and Whole Breast Ultrasound. Tomosynthesis, three-dimensional (3-D) mammography ...
(Date:11/24/2015)... Colo. , Nov. 24, 2015  Array ... that its Chief Executive Officer, Ron Squarer ... Healthcare Conference in New York.  The public is ... webcast on the Array BioPharma website.Event:Piper Jaffray Annual ... , Wednesday, December 2, 2015Time:1:30 p.m. Eastern Time ...
Breaking Medicine Technology: