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Published on: January 29, 2019
Advances in Targeting RET-Dependent Cancers
Vivek Subbiah1,2,3, Gilbert J Cote4
1Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. vsubbiah@mdanderson.org.
Abstract:
RET alterations have been characterized as oncogenic drivers in multiple cancers. The clinical validation of highly selective RET inhibitors demonstrates the utility of specific targeting of aberrantly activated RET in patients with cancers such as medullary thyroid cancer or non-small cell lung cancer. The remarkable responses observed have opened the field of RET-targeted inhibitors. In this review, we seek to focus on the impact of therapeutic RET targeting in cancers. SIGNIFICANCE: Successful clinical translation of selective RET inhibitors is poised to alter the therapeutic landscape of altered cancers. Questions that clearly need to be addressed relate to the ability to maintain long-term inhibition of tumor cell growth, how to prepare for the potential mechanisms of acquired resistance, and the development of next-generation selective RET inhibitors.
Insights
Targeting RET alterations with specific inhibitors shows promise for treating cancers like medullary thyroid and non-small cell lung cancer. Future research will focus on overcoming resistance and developing next-generation RET inhibitors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- RET alterations are key drivers in various cancers, including medullary thyroid cancer and non-small cell lung cancer.
- Highly selective RET inhibitors have shown clinical efficacy, validating RET as a therapeutic target.
Purpose of the Study:
- To review the impact of therapeutic RET targeting in cancer treatment.
- To highlight the clinical success and future directions of RET-targeted therapies.
Main Methods:
- Literature review of studies on RET alterations and RET inhibitors.
- Analysis of clinical trial data and outcomes for RET-targeted therapies.
- Discussion of challenges and future research avenues in RET inhibition.
Main Results:
- Selective RET inhibitors have demonstrated significant clinical responses in patients with RET-altered cancers.
- The success of current inhibitors opens new avenues for RET-targeted drug development.
- Acquired resistance and long-term efficacy are critical areas for ongoing investigation.
Conclusions:
- Therapeutic RET targeting is transforming the treatment landscape for specific cancers.
- Addressing acquired resistance and developing next-generation inhibitors are crucial for sustained clinical benefit.
- RET-targeted therapies represent a significant advancement in precision oncology.
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