Featured Research

from universities, journals, and other organizations

Novel test identifies patients most likely to benefit from ALK inhibition therapy

Date:
December 12, 2012
Source:
Elsevier
Summary:
Approximately one in 20 patients with non-small cell lung carcinoma (NSCLC) has chromosomal aberrations targeting the anaplastic lymphoma kinase (ALK) gene. This has considerable implications for treatment because these patients are highly responsive to ALK-specific kinase inhibitors such as crizotinib. However, current diagnostic tests have limitations. Researchers have now developed and tested a promising new method for screening ALK fusions in NSCLC. This new diagnostic assay offers a cost-effective and easy-to-perform alternative to existing tests.

Approximately one in 20 patients with non-small cell lung carcinoma (NSCLC) has chromosomal aberrations targeting the anaplastic lymphoma kinase (ALK) gene. This has considerable implications for treatment because these patients are highly responsive to ALK-specific kinase inhibitors such as crizotinib. However, current diagnostic tests have limitations. Researchers have now developed and tested a promising new method for screening ALK fusions in NSCLC. This new diagnostic assay offers a cost-effective and easy-to-perform alternative to existing tests.

The study is published in The Journal of Molecular Diagnostics.

Crizotinib is a protein tyrosine kinase inhibitor approved by the FDA for the treatment of locally advanced or metastatic ALK-positive NSCLC as detected by an FDA-approved test and is undergoing phase III clinical trials. It is crucial to the clinical success of ALK inhibitors to identify those patients most likely to benefit from ALK inhibition. The latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology now recommend upfront ALK screening for all patients with NSCLC.

There are several clinically validated methodologies currently available for the detection of ALK fusions, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcription-polymerase chain reaction (RT-PCR). Crizotinib-centered clinical trials currently utilize a FISH-based test that was recently approved by FDA as the standard companion diagnostic test for crizotinib. However, it is complex and has considerable limitations in terms of cost and throughput, making it difficult to screen large numbers of patients.

"The FISH assay has undergone extensive validation in clinical setting and is currently the gold standard for ALK fusion detection," say lead investigators Dong-Wan Kim, MD, PhD, Seoul National University Hospital, Seoul, South Korea, and Mao Mao, MD, PhD, Pfizer Oncology, California. "A disadvantage of this diagnostic assay, however, lies in the fact that the signal can be subtle and consequently hard to interpret, requiring specialized technical expertise. It is also considerably more expensive compared with IHC and RT-PCR."

In the early phase trial of crizotinib, approximately 1500 patients were screened by FISH to identify 82 ALK-positive patients. The large number of patients qualifying for screening underscores the need for a high throughput and cost- effective screening modality. "An optimal assay should therefore not only be sensitive and specific, but also be economical, easy to perform, preferably automated, and readily adaptable to workflows of clinical service laboratories," continue the investigators.

To explore alternative screening modalities for detecting ALK fusions, they designed a novel method for detecting ALK fusions by direct, multiplexed transcript profiling using the gene expression platform from NanoString. They tested their assay in 66 archival NSCLC samples which had been independently tested by both FISH and IHC methods in terms of sensitivity, specificity, reproducibility, and concordance to prior FISH and IHC.

The results were highly concordant to previous results obtained by FISH and IHC and the investigators were able to successfully detect low-level ALK fusion transcripts in samples with low tumor cell content. All samples predicted to be positive in the assay responded favorably to crizotinib.

"While further testing on a larger sample size is needed for this assay to be considered in clinical practice, we have demonstrated that it offers a cost-effective, easy to perform, high-throughput, and FFPE-compatible screening alternative for detecting ALK fusions," conclude the investigators.


Story Source:

The above story is based on materials provided by Elsevier. Note: Materials may be edited for content and length.


Journal Reference:

  1. Maruja E. Lira, Tae Min Kim, Donghui Huang, Shibing Deng, Youngil Koh, Bogun Jang, Heounjeong Go, Se-Hoon Lee, Doo Hyun Chung, Woo Ho Kim, Eric F.P.M. Schoenmakers, Yoon-La Choi, Keunchil Park, Jin Seok Ahn, Jong-Mu Sun, Myung-Ju Ahn, Dong-Wan Kim, Mao Mao. Multiplexed Gene Expression and Fusion Transcript Analysis to Detect ALK Fusions in Lung Cancer. The Journal of Molecular Diagnostics, 2012; DOI: 10.1016/j.jmoldx.2012.08.006

Cite This Page:

Elsevier. "Novel test identifies patients most likely to benefit from ALK inhibition therapy." ScienceDaily. ScienceDaily, 12 December 2012. <www.sciencedaily.com/releases/2012/12/121212130758.htm>.
Elsevier. (2012, December 12). Novel test identifies patients most likely to benefit from ALK inhibition therapy. ScienceDaily. Retrieved April 17, 2014 from www.sciencedaily.com/releases/2012/12/121212130758.htm
Elsevier. "Novel test identifies patients most likely to benefit from ALK inhibition therapy." ScienceDaily. www.sciencedaily.com/releases/2012/12/121212130758.htm (accessed April 17, 2014).

Share This



More Health & Medicine News

Thursday, April 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Thousands Of Vials Of SARS Virus Go Missing

Thousands Of Vials Of SARS Virus Go Missing

Newsy (Apr. 16, 2014) A research institute in Paris somehow misplaced more than 2,000 vials of the deadly SARS virus. Video provided by Newsy
Powered by NewsLook.com
Formerly Conjoined Twins Released From Dallas Hospital

Formerly Conjoined Twins Released From Dallas Hospital

Newsy (Apr. 16, 2014) Conjoined twins Emmett and Owen Ezell were separated by doctors in August. Now, nearly nine months later, they're being released from the hospital. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins