RET rearrangements in non–small cell lung cancer and implications for the future of precision drug development

ABSTRACT

Introduction: Over the past years, we have witnessed the discovery of several oncogenic driver mutations, and the emergence of specific inhibitors with high response rates and few treatment-related adverse events. RET-rearranged lung cancers represent a small subset of lung cancers, most commonly encountered in patients with adenocarcinoma and minimal or no exposure to tobacco. Several multikinase inhibitors have been tested with high ‘off-target’ toxicity and low RET inhibition activity.

Areas covered: Here, we review the main aspects of the biology of RET, the challenges of RET inhibition in lung cancers, clinical data from several multikinase inhibitors, and some future perspectives with regard to precision oncology.

Expert commentary: Early phase clinical trials results of more selective RET inhibitors are eagerly awaited.

KEYWORDS:

• RET-rearrangement
• NSCLC
• lung cancers
• KIF5B-RET
• RET mutation

Declaration of Interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.