RET signaling pathway and RET inhibitors in human cancer

Regua, Angelina T.; Najjar, Mariana; Lo, Hui-Wen

doi:10.3389/fonc.2022.932353

Cited by 38 publications

(32 citation statements)

References 264 publications

(325 reference statements)

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“…The proto-oncogene RET encodes a membrane receptor tyrosine kinase involved in many cellular processes, including the development of the central nervous system, peripheral nervous system, and kidney ( 11 , 12 ). RET fusions are activated in a ligand-independent manner, promoting cancer cell proliferation and survival ( 13 ). As a result, RET fusion proteins have become an attractive target for precision medicine.…”

Section: Introductionmentioning

confidence: 99%

RET rearrangement-positive pancreatic cancer has remarkable response to pralsetinib: a case report

et al. 2023

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Patients with metastatic pancreatic cancer have limited treatment options and a dismal prognosis. While RET fusion is rare (0.6%) in pancreatic cancer, the efficacy of RET-targeted treatment in patients with TRIM33-RET fusion has not been previously reported. Herein, we presented a case of a 68-year-old man with pancreatic cancer harboring TRIM33-RET fusion who responded remarkably to pralsetinib despite being intolerant to chemotherapy. To our knowledge, this is the first report on the clinical value of a single TRIM33-RET fusion in pancreatic cancer, which may benefit from the targeted therapy.

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Section: Introductionmentioning

confidence: 99%

RET rearrangement-positive pancreatic cancer has remarkable response to pralsetinib: a case report

et al. 2023

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“… 13 Most RET fusion proteins lack a transmembrane domain and are chimeric cytosolic proteins that exert their oncogenic influence via constitutive activation of RET kinase domain. 14 This enhances activity of various downstream signaling pathways including phosphatidylinositol-3-kinase/protein kinase B, RAS/RAF, and mitogen activated protein kinase, 13 , 14 which, in turn, increase cell proliferation, survival, migration, and differentiation ( Figure 1 ). 13 …”

Section: Ret Rearrangements and Molecular Testingmentioning

confidence: 99%

RET Fusion-Positive Non-small Cell Lung Cancer: The Evolving Treatment Landscape

et al. 2023

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The objective of this narrative review is to summarize the efficacy and safety of available therapies for rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), including in patients with central nervous system (CNS) metastases. Background information is provided on RET rearrangements in NSCLC and the molecular testing options available as well as an overview of clinical guidelines for molecular testing, which recommend broad molecular testing, including for RET rearrangements. The efficacy and safety of potential treatments for RET fusion-positive NSCLC, including multikinase inhibitors, RET-selective inhibitors, pemetrexed-based therapy, and immunotherapies are reviewed from Phase I/II and `real-world’ studies, alongside an overview of primary and secondary resistance mechanisms. The RET-selective inhibitors, selpercatinib and pralsetinib, are preferred first-line therapy options for patients with RET fusion-positive metastatic NSCLC and are recommended as subsequent therapy if RET inhibitors have not been used in the first-line setting.

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“…154,155 Thus, long-term monitoring will be crucial to identify any potential adverse effects on the development and function of neurons following suppression of RET activity. 156…”

Section: Mechanism Of Reti-induced Hypertensionmentioning

confidence: 99%

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

et al. 2023

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Cardiovascular disease and cancer are 2 of the leading causes of death worldwide. Although improvements in outcomes have been noted for both disease entities, the success of cancer therapies has come at the cost of at times very impactful adverse events such as cardiovascular events. Hypertension has been noted as both, a side effect as well as a risk factor for the cardiotoxicity of cancer therapies. Some of these dynamics are in keeping with the role of hypertension as a cardiovascular risk factor not only for heart failure, but also for the development of coronary and cerebrovascular disease, and kidney disease and its association with a higher morbidity and mortality overall. Other aspects such as the molecular mechanisms underlying the amplification of acute and long-term cardiotoxicity risk of anthracyclines and increase in blood pressure with various cancer therapeutics remain to be elucidated. In this review, we cover the latest clinical data regarding the risk of hypertension across a spectrum of novel anticancer therapies as well as the underlying known or postulated pathophysiological mechanisms. Furthermore, we review the acute and long-term implications for the amplification of the development of cardiotoxicity with drugs not commonly associated with hypertension such as anthracyclines. An outline of management strategies, including pharmacological and lifestyle interventions as well as models of care aimed to facilitate early detection and more timely management of hypertension in patients with cancer and survivors concludes this review, which overall aims to improve both cardiovascular and cancer-specific outcomes.

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RET signaling pathway and RET inhibitors in human cancer

Cited by 38 publications

References 264 publications

RET rearrangement-positive pancreatic cancer has remarkable response to pralsetinib: a case report

RET rearrangement-positive pancreatic cancer has remarkable response to pralsetinib: a case report

RET Fusion-Positive Non-small Cell Lung Cancer: The Evolving Treatment Landscape

Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

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