REToma: a cancer subtype with a shared driver oncogene

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• The REarranged during Transfection (RET) gene encodes a receptor tyrosine kinase crucial for cell signaling.
• RET alterations, including gene fusions and mutations, act as driver oncogenes in multiple human cancers.
• RET tyrosine kinase inhibitors (TKIs) demonstrate therapeutic efficacy in RET-driven cancers like thyroid and lung cancer.

Purpose of the Study:

• To investigate the potential of RET alterations as a unifying biomarker across diverse cancer types.
• To evaluate the therapeutic implications of targeting RET in cancers beyond thyroid and lung malignancies.
• To propose a novel classification and treatment strategy for RET-altered cancers.

Main Methods:

• Review of existing literature on RET gene alterations in various human cancers.
• Analysis of oncogenic mutation patterns within RET's extracellular and kinase domains.
• Correlation of RET alteration status with clinical responses to RET-targeted therapies.

Main Results:

• RET fusions are identified in papillary thyroid, lung, colorectal, pancreatic, and breast cancers.
• Activating RET mutations, similar to those in medullary thyroid cancer, are found in lung, colorectal, and breast cancers.
• These RET alterations are predicted to confer sensitivity to RET TKIs in a broad range of cancers.

Conclusions:

• Cancers driven by oncogenic RET alterations can be collectively termed 'REToma'.
• A tissue-agnostic therapeutic approach using RET TKIs is proposed for 'REToma'.
• Targeting RET offers a promising strategy for a subset of lung, colorectal, breast, and other cancers.