Cancer treatment has advanced with the development of precision therapies targeting proto-oncogene alterations. One such proto-oncogene is RET, which encodes a receptor tyrosine kinase involved in embryonic development.

Activating RET alterations have been identified as oncogenic drivers in various tumor types. The ret proto-oncogene (RET) is activated by 2 main mechanisms, ie, sporadic or germline mutations that activate the kinase domain and chromosomal rearrangements that fuse the kinase domain with upstream gene fragments, thereby leading to constitutive activation.

RET mutations occur in more than 95% of germline medullary thyroid cancer cases and approximately 50% of sporadic cases. By contrast, RET fusions occur in papillary thyroid cancer, accounting for up to 40% of sporadic cases and appearing at a higher frequency after radioiodine exposure. RET fusions also occur in nearly 1% to 2% of NSCLC cases and are associated with a high risk of brain metastases. Other tumor types associated with RET fusions (incidence <1%) include pancreatic, colorectal, ovarian, and salivary gland cancers.

Selective RET inhibitors have been shown to provide deep and durable responses in patients with RET alterations. Tumor-agnostic RET inhibition lends support for universal screening of solid tumors for RET alterations, preferably via tissue-based, next-generation sequencing and can be used to detect RET mutations and fusions.

Which patients do you screen for RET alterations, and what is your preferred method of screening?