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RET Mutations May Emerge as New Target for Lung Cancer Treatments

RET Mutations May Emerge as New Target for Lung Cancer Treatments | Lung Cancer Dispatch | Scoop.it

A certain type of mutation in a protein, called RET, occurs in a significant subset of lung cancer patients, a recent study shows. Known as 'rearrangements,' these mutations fuse the RET gene with other nearby genes, resulting in a RET protein that contains parts of other proteins and is hyperactive. Patients with similar rearrangement mutations in another gene, ALK, can experience drastic improvements from treatment with ALK inhibitors such as crizotinib (Xalkori). This raises the hope that patients with RET rearrangement mutations may be similarly helped by drugs that block RET–either novel RET inhibitors or existing tyrosine kinase inhibitors (TKIs), such as vandetanib (Caprelsa), sunitinib (Sutent), sorafenib (Nexavar), or ponatinib (Iclusig). Identifying patients who may benefit from such treatments would be made easier by the new test for RET mutations developed by the study’s authors. When examining a group of patients with lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC), who did not have mutations in other cancer-relevant genes, the researchers found that 15% had RET rearrangement mutations.

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Medical Xpress | June 3, 2013

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New Drug May Be Effective for Lung Cancer Patients with RET Mutations

New Drug May Be Effective for Lung Cancer Patients with RET Mutations | Lung Cancer Dispatch | Scoop.it

Some patients with non-small cell lung cancer (NSCLC) have tumor mutations called "RET fusions." RET fusions are especially common in patients who have adenocarcinoma, never smoked, and/or have no mutations in other genes commonly associated with NSCLC. In an ongoing phase II clinical trial, three patients with adenocarcinoma and RET fusions appeared to respond well to the drug cabozantinib (Cometriq). The tumors of two of the patients shrank during Cometriq treatment, while the third experienced stable disease. Further studies are needed, but these results suggest that Cometriq may be an effective treatment for NSCLC patients with RET fusions. Research paper: http://cancerdiscovery.aacrjournals.org/content/early/2013/03/23/2159-8290.CD-13-0035.abstract

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Cancer Discovery | Mar 26, 2013

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Iclusig Inhibits Mutant Proteins Found in Lung Cancer

The leukemia drug ponatinib (Iclusig) also appears to target mutant versions of two proteins involved in non-small cell lung cancer (NSCLC). This is supported by two recent studies in which Iclusig slowed the growth of cells with mutant RET and FGFR proteins. The drug also shrank tumors with RET mutations that had been grown in mice. Based on these findings, Iclusig manufacturer ARIAD Pharmaceuticals is planning a phase II clinical trial to investigate the drug's effectiveness against NSCLC with RET mutations. A phase II trial assessing Iclusig's effects in squamous cell carcinoma (SCC) of the lung with FGFR mutations is already underway at the Dana-Farber Cancer Institute, Boston, Massachusetts, and is currently enrolling participants.

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ARIAD Pharmaceuticals, Inc. | Apr 8, 2013

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