Lung cancer patients can be screened for ALK-inhibitor suitability

Aug 8 2012

By Andrew Czyzewski

Anaplastic lymphoma kinase (ALK) gene status in patients with lung adenocarcinoma can be determined non-invasively using circulating tumor cells (CTCs), research shows.

Since patients with altered ALK show "an outstanding favourable response" to targeted inhibition, the findings support routine prescreening in lung cancer patients, say Paul Hofman (University of Nice Sophia Antipolis, France) and colleagues.

Genomic alteration involving the ALK gene is found in 1-7% of non-small-cell lung cancers (NSCLCs). Patients with tumors with ALK rearrangement tend to be younger, more frequently males, and never smokers than those without.

These individuals may have excellent response to the ALK small-molecule inhibitor, crizotinib. However, invasive lung biopsy is currently required to ascertain ALK status and often there is insufficient material.

"Treatment with crizotinib has to be restricted to tumours with a proven ALK gene rearrangement, which implies a systematic prescreening of tumour samples with the reliable technical approaches," Hofman et al explain in the Annals of Oncology.

The team recently demonstrated that CTCs can be isolated by different methods even in early-stage disease in patients undergoing surgery for lung carcinomas. Moreover, the presence and the number of CTCs were associated with worse prognosis.

However, assessment of ALK status in CTCs, and whether this corresponds to ALK status in tumor tissue, has never been performed.

The researchers therefore recruited 87 patients with lung adenocarcinoma and assessed their ALK status both in tumor samples and in CTCs using an assay based on a dual immunochemical and fluorescence in situ hybridisation (FISH) approach for ALK gene rearrangement.

A total of five patients showed ALK gene rearrangement and strong ALK protein expression in CTCs and corresponding tumor samples. Both ALK-FISH and ALK immunoreactivity analyzes gave negative results in CTCs and corresponding tumor samples for 82 patients.

"We can, thus, speculate that CTCs harbouring this specific genomic alteration have facilitated migration and represent an aggressive set of tumour cells," Hofman et al comment.

They note that a quantitative real-time PCR approach has been recently developed to quantify ALK transcripts, which could pave the way for prescreening of patients with lung cancer.

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