Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Not all lung cancer patients who could benefit from crizotinib are identified by FDA-approved test

29.08.2012
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.

Garth Sundem | EurekAlert!
Further information:
http://www.ucdenver.edu

More articles from Health and Medicine:

nachricht Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>