Navigation Links
Not all lung cancer patients who could benefit from crizotinib are identified by FDA-approved test
Date:8/28/2012

Break apart a couple worm-like chromosomes and they may reconnect with mismatched tips and tails such is the case of the EML4-ALK fusion gene that creates 2-7 percent of lung cancers. Almost exactly a year ago, the FDA approved the drug crizotinib to treat these ALK+ lung cancer patients, who were likely never smokers. Informed doctors use the test called a FISH assay to check for the EML4-ALK fusion gene, and then if the test is positive, ALK+ patients benefit greatly from crizotinib.

A recent University of Colorado Cancer Center case study published in the Journal of Thoracic Oncology describes the never-before-seen case of a patient who tested negative for EML4-ALK fusion based on the well-defined criteria for FISH assay as approved by FDA, but nevertheless experienced remission after treatment with crizotinib.

"The case implies that not all patients who might benefit from the drug are captured by the FDA-approved FISH assay. Perhaps despite the FDA pairing of crizotinib with FISH, other assays or other criteria for ALK/FISH positivity could be used," says paper co-author, Fred R. Hirsch, MD, PhD, investigator at the CU Cancer Center and professor of medical oncology and pathology at the CU School of Medicine.

In fact, it was by chance that after the patient's negative FISH, Hirsch and colleagues chose to look deeper. Besides using FISH to stain sections of chromosomes with the EML4-ALK fusion gene, the team used immunohistochemistry to look for the protein products of this fusion gene not the faulty plans but the faulty results. Sure enough, in this case, the patient had the EML4-ALK fusion protein but apparently without the typical EML4-ALK fusion gene that should code for it.

The team looked deeper, using next-gen sequencing to discover what, exactly, was going on in the short arm of chromosome number 2, which harbors the EML4-ALK fusion gene. What they found looked less like a pair of clean breaks that reattached in the wrong places say, like a snapped radius and ulna that found the wrong reattachments to make a rulna and an ulnius but more like shattered fragments with genetic shards embedded in and around the primary sections.

"We think these genetic shards made the resulting gene look different enough from the typical EML4-ALK fusion gene to avoid detection by the FDA approved FISH assay," Hirsch says.

Within two weeks of starting crizotinib, the patient reported improved pain symptoms and energy. Four months after starting the drug, a PET scan, which shows the sugar signatures of rapidly developing cancer cells, was negative. A chest CT scan showed the primary tumor had shrunk by 75 percent.

"Certainly FISH is a valuable assay to check for ALK-positive lung cancer," Hirsch says. "But we hope this work demonstrates the need to further refine this test, to ensure that all the patients who could benefit from crizotinib in fact receive the drug."

Together with CU Cancer Center colleagues including Drs. Doebele, Garcia, Aisner and Camidge, Hirsch is participating in a larger study comparing different assays for ALK testing to determine which assay or combination of assays identifies the most patients likely to benefit from crizotinib.


'/>"/>
Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

Related medicine news :

1. Breast Cancer Drug Might Help Men on Prostate Cancer Therapy
2. Reducing the side effects of treatment for prostate cancer
3. Accuracy of narrow band imaging with colonoscopy allows for distal non-cancerous polyps to be left in place
4. Daily Aspirin May Help Fight Prostate Cancer, But Not Breast Cancer
5. WSU researcher documents links between nutrients, genes and cancer spread
6. Excess Pounds Raise Risk of Breast Cancer Recurrence, Death: Study
7. Johns Hopkins team finds ICU misdiagnoses may account for as many annual deaths as breast cancer
8. Compounds activate key cancer enzyme to interfere with tumor formation
9. Lack of sleep found to be a new risk factor for aggressive breast cancers
10. Cancer vaccine Special Focus series published in Human Vaccines & Immunotherapeutics
11. Obese and overweight women face increased risk of recurrence of most common type of breast cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... ... TherapySites, the leading website and online marketing ... Association. This new relationship allows TherapySites to continue to extend their online ... and promotional offers. , "TCA is extremely excited about this new partnership, as ...
(Date:6/27/2016)... ... ... TopConsumerReviews.com recently awarded their highest five-star rating to Best Buy Eyeglasses, an ... United States and Canada wear eyeglasses. Once considered to be a purely functional part ... fashion statement. Even celebrities use glasses as a way of creating an iconic image—like ...
(Date:6/26/2016)... ... June 26, 2016 , ... Pixel Film Studios Released ProSlice Levels, ... editors can give their videos a whole new perspective by using the title ... Pixel Film Studios. , ProSlice Levels contains over 30 Different presets to choose ...
(Date:6/26/2016)... ... June 26, 2016 , ... Many women are confused ... endometriosis. These women need a treatment plan to not only alleviate symptoms and ... help for preservation of fertility and ultimately achieving a pregnancy. The specialists at ...
(Date:6/25/2016)... ... , ... The temporary closing of Bruton Memorial Library on June 21 due to a possible ... often overlooked aspect of head lice: the parasite’s ability to live away from a human ... but a necessary one in the event that lice have simply gotten out of control. ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... -- , , , WHEN: , ... , , , LOCATION: , , , Online, with free ... EXPERT PANELISTS:  , , , Frost & Sullivan,s Global Vice President ... Industry Analyst, Divyaa Ravishankar and Unmesh Lal, Program Manager , ... is witnessing an exceptional era. Several new demand spaces, such as ...
(Date:6/23/2016)... , June 23, 2016  Guerbet announced today ... Inc.,s Supplier Horizon Award . One ... Guerbet was recognized for its support of Premier members ... through clinical excellence, and commitment to lower costs. ... receive this recognition of our outstanding customer service from ...
(Date:6/23/2016)... -- The Biotechnology industry might still be ... opportunities to investors. Stock-Callers.com assesses the recent performances of ... XON ), Vertex Pharmaceuticals Inc. (NASDAQ: ... ), and Regeneron Pharmaceuticals Inc. (NASDAQ: REGN ... complimentary trade alerts at: http://stock-callers.com/registration ...
Breaking Medicine Technology: