Evidence map›Paper›PMID 38997570›Full record

ReviewDrugs2024

RET Inhibitors in RET Fusion-Positive Lung Cancers: Past, Present, and Future.

Monica F Chen, Matteo Repetto, Clare Wilhelm, Alexander Drilon

Abstract readReview
In one paragraph

Review in Drugs, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Genes · 2025
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Monica F Chen *Thoracic Oncology, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-7485-2463
Matteo Repetto *Early Drug Development Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Clare WilhelmThoracic Oncology, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
Alexander DrilonThoracic Oncology, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA. drilona@mskcc.org.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Investigational Cancer Therapeutics Training Program (ICTTP)T32CA009207 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Omar Abdel-Wahab, Alexander Drilon · 1985 to 2026
$13.7M
Integration of Imaging and Circulating Plasma Cell-Free DNA Sequencing Using MSK-ACCESS to Monitor Treatment Response and Predict Progression in Patients With Multiple Cancers on Targeted TherapyR01CA273224 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Michael F. Berger, Alexander Drilon · 2022 to 2026
$3.6M
Predicting sensitivity and resistance in RET-driven cancersR01CA251591 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI DRILON, ALEXANDER · 2021 to 2025
$2.0M
American Society of Clinical Oncology ASCO Young Investigator AwardNational Cancer Center P30CA008748National Cancer Center R01CA251591National Cancer Center R01CA273224-01National Cancer Center T32-CA009207NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA251591NCI NIH HHS R01 CA273224NCI NIH HHS T32 CA009207
6 · The paper itself

Abstract

While activating RET fusions are identified in various cancers, lung cancer represents the most common RET fusion-positive tumor. The clinical drug development of RET inhibitors in RET fusion-positive lung cancers naturally began after RET fusions were first identified in patient tumor samples in 2011, and thereafter paralleled drug development in RET fusion-positive thyroid cancers. Multikinase inhibitors were initially tested with limited efficacy and substantial toxicity. RET inhibitors were then designed with improved selectivity, central nervous system penetrance, and activity against RET fusions and most RET mutations, including resistance mutations. Owing their success to these rationally designed features, the first-generation selective RET tyrosine kinase inhibitors (TKIs) had higher response rates, more durable disease control, and an improved safety profile compared to the multikinase inhibitors. This led to lung and thyroid cancer, and later tumor-agnostic regulatory approvals. While next-generation RET TKIs were designed to abrogate uncommon on-target (e.g., solvent front mutation) resistance to selpercatinib and pralsetinib, many of these drugs lacked the selectivity of the first-generation TKIs, raising the question of what the future holds for drug development in RET-dependent cancers.

Indexed as

Lung NeoplasmsProtein Kinase InhibitorsProto-Oncogene Proteins c-retAntineoplastic AgentsHumansMutationOncogene Proteins, FusionPyrazolesPyridinesPyrimidinesAntineoplastic AgentsOncogene Proteins, FusionpralsetinibProtein Kinase InhibitorsProto-Oncogene Proteins c-retPyrazolesPyridinesPyrimidinesRET protein, humanselpercatinib

Identifiers

PMID38997570
PMCPMC11977511

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.