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RET alterations: actionable oncogenic drivers across multiple tumor types

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?

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    I order solid and liquid NGS panel on all metastatic and locally advanced solid tumors . RET is one of the markers.
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    I also do NGS panel testing in all metastatic patients and this includes RET alterations
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    I try to get NGS that also detects RET fusions in all patients with non-small lung cancer Stage IB and above. I would also check in other disease typed refractory to initial lines of therapy.
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    Yes. Standard NGS ON tissue and liquid NGS in this day and age to base treatment on NGS findings

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    Source : https://too.pa

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    Everyone gets NGS- typically tissue and blood if able. I agree with colleagues as stated.
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    I do NGS testing on all metastatic pts, which include RET testing in the panel
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    I order it in all metastatic patients. I prefer RET testing as part of NGS.
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    I order RET testing for all patients with metastatic solid tumors (e.g. lung, breast, colon, etc, etc).
  • 1yr
    I order it in all metastatic patients. I prefer RET testing as part of NGS.
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    I order it in all metastatic patients. I prefer RET testing as part of NGS.
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    All metastatic patients and I use ngs with dna and rna based testing. This could be done on tissue of plasma
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    I order tissue and liquid NGS on all advanced pts looking for RET fusions/alteratons. Will repeat liquid NGS on progression as well.
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    Currently it is standard in our oncology practice to send for tissue NGS testing and/or liquid NGS for any patient with advanced solid malignancy at time of diagnosis. RET mutations are quite rare in lung cancer patients though.
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    We do order an NGS panel either at initial presentation with metastatic disease and in relapse. Both tissue (initial) and liquid (initial and subsequent). Hopefully this can catch RET mutations. RNA and DNA sequencing both preferred
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    I tend to test all stage IV patients with tIssue NGS - which includes RET mutations and activations. If there is not tissue or enough tissue then we order liquid NGS. Any solid organ malignancy that has a RET Mutation would be eligible for targeted therapy.
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    I think all patients should be screened for RET as any targeted therapy will be superior to standard chemotherapy. I use NGS
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    I check all stage iv solid cancers RET testing along with other mutations on NGS that Dos DNAand RNA testing, prefer tissue biopsy
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    I test all patients with metastatic disease and I use next gen universally
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    We do order an NGS panel either at initial presentation with metastatic disease and in relapse. Both tissue and liquid. Hopefully this can catch RET mutations and then use therapy post SOC.
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    I test all metastatic solid tumors with NGS DNA and RNA panel that includes RET, tissue if available and liquid if not. For nonmetastatic, RET inhibitors are not yet approved
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    I typically order an ngs panel either at initial presentation with metastatic disease and in first relapse. the ngs panel includes whole exome and transcriptome panel, preferably on tissue +/- plasma based testing.
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    I test all stage IV cancers and most locally advanced cancers with no local therapy options with NGS which includes RET mutations and fusions, now we are checking NGS before using neoadjuvant chemo-immunotherapy in early-stage Non small cell lung caners. I use the Next Gen Sequencing platform with both DNA and RNA sequencing as fusions are better detected on RNA sequencing.

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