☆ 4.6 Review

Research Progress on RET Fusion in Non-Small-Cell Lung Cancer

FRONTIERS IN ONCOLOGY (2022)

Related references

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Article Oncology

Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States

Lisa M. Hess et al.

Summary: The study revealed that patients with RET fusions have more favorable overall survival rates, but after adjusting for baseline covariates, there were no significant differences in either OS or PFS based on RET status among patients treated with standard therapy.

BMC CANCER (2021)

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Review Oncology

Diagnostics, therapeutics and RET inhibitor resistance for RET fusion?positive non-small cell lung cancers and future perspectives

Chang Lu et al.

Summary: This article summarizes the current hot topic of selective RET inhibitors and outlines the utility of various diagnostic techniques, as well as the management evidence for RET fusion-positive NSCLC patients, including specific patient groups and mechanisms of acquired resistance.

CANCER TREATMENT REVIEWS (2021)

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Article Cell Biology

RET inhibition in novel patient-derived models of RET fusion-positive lung adenocarcinoma reveals a role for MYC upregulation

Takuo Hayashi et al.

Summary: The study demonstrates that cabozantinib is effective in targeting lung cancers with RET rearrangements by inhibiting tumor growth and activating specific apoptotic pathways. Additionally, cabozantinib suppresses MYC protein levels induced by RET expression, suggesting new therapeutic strategies for RET fusion-driven lung cancers. The novel RET fusion-dependent preclinical models offer valuable tools for refining current therapies and exploring new treatment approaches.

DISEASE MODELS & MECHANISMS (2021)

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Article Oncology

Anti-epidermal growth factor vaccine antibodies increase the antitumor activity of kinase inhibitors in ALK and RET rearranged lung cancer cells

Jordi Codony-Servat et al.

Summary: The study indicates that anti-EGF antibodies generated by vaccination can enhance the antitumor activity of TKIs in ALK and RET-positive NSCLC cell lines, improving the efficacy of kinase inhibitors and delaying the emergence of resistant clones. This suggests that combining EGF vaccine with ALK and RET TKIs in clinical trials may be beneficial for advanced NSCLC patients with EML4-ALK and CCDC6-RET rearrangements.

TRANSLATIONAL ONCOLOGY (2021)

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Article Oncology

Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations

V Subbiah et al.

Summary: The study revealed that RET mutations resistant to selpercatinib and pralsetinib mainly located at the solvent front and hinge regions in medullary thyroid cancer and non-small-cell lung cancer. The unconventional binding mode of selpercatinib and pralsetinib to RET avoids interference from gatekeeper mutations but is susceptible to non-gatekeeper mutations.

ANNALS OF ONCOLOGY (2021)

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Letter Oncology

A Novel Oncogenic RET Fusion Variant in NSCLC: RELCH-RET

Scott P. Myrand

JOURNAL OF THORACIC ONCOLOGY (2021)

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Review Biochemistry & Molecular Biology

Novel Emerging Molecular Targets in Non-Small Cell Lung Cancer

Sara Elena Rebuzzi et al.

Summary: In the systemic treatment of advanced NSCLC patients, targeted therapies such as EGFR, ALK, ROS1, and BRAF inhibitors have been significant breakthroughs. In addition to these known molecular drivers, potential therapeutic targets including MET, RET, NTRK, KRAS, PIK3CA, and HER2 are rapidly emerging. Research on these emerging molecular targets is crucial to increasing the proportion of patients benefiting from tailored therapeutic approaches.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Oncology

Non-Small Cell Lung Cancer, Version 2.2021 Featured Updates to the NCCN Guidelines

David S. Ettinger et al.

Summary: The NCCN Guidelines for NSCLC cover all aspects of management, with recent updates focusing on targeted therapies, immunotherapies, and their respective biomarkers.

JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK (2021)

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Review Oncology

Chasing the Target: New Phenomena of Resistance to Novel Selective RET Inhibitors in Lung Cancer. Updated Evidence and Future Perspectives

Sara Fancelli et al.

Summary: This review discusses recent knowledge on RET resistance in NSCLC and the development of new drugs or drug combinations. While pralsetinib and selpercatinib are effective against NSCLC, there is a need for the next generation of TKIs to overcome adaptive mutations. Co-occurring amplifications of KRAS and MET may also present additional mechanisms of resistance to direct inhibition.

CANCERS (2021)

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Editorial Material Oncology

Rethinking treatment for RET-altered lung and thyroid cancers: selpercatinib approval by the EMA

C. M. Della Corte et al.

ESMO OPEN (2021)

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Article Oncology

Cancer statistics for the year 2020: An overview

Jacques Ferlay et al.

Summary: The study briefly reviews the methods and data sources used in compiling the IARC GLOBOCAN cancer statistics for 2020 and summarizes the main results. It estimated that there were nearly 19.3 million new cancer cases and almost 10 million cancer deaths worldwide in 2020, with the most commonly diagnosed cancers being female breast cancer and lung cancer, and the most common causes of cancer death being lung cancer and liver cancer.

INTERNATIONAL JOURNAL OF CANCER (2021)

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Review Oncology

Therapeutic strategies in RET gene rearranged non-small cell lung cancer

Leylah M. Drusbosky et al.

Summary: Recent FDA approvals for tumor-agnostic drugs have shifted cancer treatment from organ/histology-specific strategies to biomarker-guided approaches. RET gene fusions, known oncogenic drivers in various tumors, can be effectively targeted by inhibitors like selpercatinib and pralsetinib, showing significant clinical benefits in NSCLC patients.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Article Oncology

Final survival results for the LURET phase II study of vandetanib in previously treated patients with RET-rearranged advanced non-small cell lung cancer

Kiyotaka Yoh et al.

Summary: The study on the efficacy and safety of vandetanib in previously treated RET-rearranged advanced NSCLC patients showed a prolonged PFS and OS, with hypertension, diarrhea, and rash acneiform being the most common adverse events.

LUNG CANCER (2021)

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Article Pharmacology & Pharmacy

Novel Human-Derived RET Fusion NSCLC Cell Lines Have Heterogeneous Responses to RET Inhibitors and Differential Regulation of Downstream Signaling

Laura Schubert et al.

Summary: The study introduced three novel RET fusion-positive non-small cell lung cancer cell lines, demonstrating their differential responses to RET inhibition and regulation of downstream signaling, offering important insights into the regulation of response to RET tyrosine kinase inhibitors and other potential therapeutic targets.

MOLECULAR PHARMACOLOGY (2021)

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Article Cell Biology

Cabozantinib Reverses Topotecan Resistance in Human Non-Small Cell Lung Cancer NCI-H460/TPT10 Cell Line and Tumor Xenograft Model

Zi-Ning Lei et al.

Summary: The study demonstrates that CBZ can inhibit the ABCG2 transporter and resensitize drug-resistant cancer cells to specific drugs, showing promising reversal effects in an in vivo xenograft model.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Oncology

Therapeutic Advances in the Management of Patients with Advanced RET Fusion-Positive Non-Small Cell Lung Cancer

Fangdi Sun et al.

Summary: Screening for activating driver gene alterations at the time of diagnosis is the standard of care for advanced non-small cell lung cancer (NSCLC). Activating RET fusions, found in approximately 1-2% of NSCLCs, are targetable driver alterations. Selpercatinib and pralsetinib are recommended as first-line therapy, with repeat tissue biopsy for delineating acquired resistance and consideration of combination inhibition if actionable resistance is identified. Maintenance chemotherapy or immunotherapy shows limited activity in RET fusion-positive NSCLC. Further research on potential resistance mechanisms and novel RET-selective TKIs is needed for rational sequential therapy in this patient population.

CURRENT TREATMENT OPTIONS IN ONCOLOGY (2021)

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Review Biochemistry & Molecular Biology

Anti-PD1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer with Actionable Oncogenic Driver Mutations

Edouard Dantoing et al.

Summary: Anti-PD1/PD-L1 immunotherapy has become a standard of care for NSCLC, with patient selection based on PD-L1 expression and tumor mutational burden. However, mutations in oncogenic drivers can impact efficacy.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Oncology

Advances in the treatment of RET-fusion-positive lung cancer

Georg Pall et al.

Summary: In recent years, two selective and potent RET-inhibitors have been approved for the treatment of patients with metastatic RET-fusion-positive lung cancer, providing hope for this patient population.

LUNG CANCER (2021)

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Review Oncology

RET Inhibitors in Non-Small-Cell Lung Cancer

Priscilla Cascetta et al.

Summary: RET rearrangements in NSCLC act as a potential therapeutic target, with selective RET inhibitors showing higher efficacy rates and good tolerability, providing hope for patients with RET-positive NSCLC. Ongoing phase III clinical trials will definitively establish the efficacy of these inhibitors in RET-positive NSCLC patients.

CANCERS (2021)

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Review Oncology

Precision therapy for RET-altered cancers with RET inhibitors

Kyaw Z. Thein et al.

Summary: RET is involved in physiological development and its activated mutations are potent drivers of cancer. Traditional treatment with MKIs has modest efficacy but notable toxicities. Novel RET inhibitors like selpercatinib and pralsetinib have shown success in the clinic, providing a promising future outlook.

TRENDS IN CANCER (2021)

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Article Pharmacology & Pharmacy

Pralsetinib for the treatment of non-small cell lung cancer

X-Y Fu et al.

Summary: RET events have been identified as oncogenic drivers in NSCLC, and the novel RET inhibitor pralsetinib has shown excellent efficacy and low toxicity in NSCLC patients.

DRUGS OF TODAY (2021)

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Article Oncology

Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program

Oliver Illini et al.

Summary: In a real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC patients and was well tolerated.

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY (2021)

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Review Oncology

ASCO 2020 non-small lung cancer (NSCLC) personal highlights

Lena Horvath et al.

Summary: This article summarizes the key highlights of the virtual ASCO 2020 meeting regarding non-small cell lung cancer (NSCLC), covering advancements in both early and advanced-stage NSCLC treatment. It emphasizes the efficacy of targeted therapies in early stage NSCLC and the importance of immunotherapy in advanced-stage disease.

MEMO-MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY (2021)

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Article Oncology

Cancer statistics, 2020

Rebecca L. Siegel et al.

CA-A CANCER JOURNAL FOR CLINICIANS (2020)

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Article Oncology

RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies

Benjamin J. Solomon et al.

JOURNAL OF THORACIC ONCOLOGY (2020)

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Article Oncology

Mechanisms of resistance to selective RET tyrosine kinase inhibitors in RET fusion-positive non-small-cell lung cancer

J. J. Lin et al.

ANNALS OF ONCOLOGY (2020)

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Editorial Material Oncology

Defining resistance mechanisms to selective RET tyrosine kinase inhibitors in RET fusion-positive non-small-cell lung cancer

L. Tan et al.

ANNALS OF ONCOLOGY (2020)

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Review Oncology

Emerging oncogenic fusions other than ALK, ROS1, RET, and NTRK in NSCLC and the role of fusions as resistance mechanisms t o targeted therapy

Kenichi Suda et al.

TRANSLATIONAL LUNG CANCER RESEARCH (2020)

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Article Oncology

Characteristics and outcomes of RET-rearranged Korean non-small cell lung cancer patients in real-world practice

Jiyun Lee et al.

JAPANESE JOURNAL OF CLINICAL ONCOLOGY (2020)

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Article Oncology

Clinical Characteristics and Molecular Patterns of RET-Rearranged Lung Cancer in Chinese Patients

Kai Zhang et al.

ONCOLOGY RESEARCH (2019)

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Review Physiology

Discovery Stories of RET Fusions in Lung Cancer: A Mini-Review

Kengo Takeuchi

FRONTIERS IN PHYSIOLOGY (2019)

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Article Oncology

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry

J. Mazieres et al.

ANNALS OF ONCOLOGY (2019)

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Article Biochemistry & Molecular Biology

Identification of nicotinamide aminonaphthyridine compounds as potent RET kinase inhibitors and antitumor activities against RET rearranged lung adenocarcinoma

Modi Wang et al.

BIOORGANIC CHEMISTRY (2019)

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Article Oncology

A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma

Toyoaki Hida et al.

LUNG CANCER (2019)

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Article Oncology

Phase 1 Study of Cabozantinib in Japanese Patients With Expansion Cohorts in Non-Small-Cell Lung Cancer

Hiroshi Nokihara et al.

CLINICAL LUNG CANCER (2019)

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Article Oncology

Immune checkpoint inhibitor treatment in patients with oncogene-addicted non-small cell lung cancer (NSCLC): summary of a multidisciplinary roundtable discussion

Anna S. Berghoff et al.

ESMO OPEN (2019)

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Article Oncology

Selective RET kinase inhibition for patients with RET-altered cancers

V. Subbiah et al.

ANNALS OF ONCOLOGY (2018)

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Review Oncology

Clinical and Translational Implications of RET Rearrangements in Non-Small Cell Lung Cancer

Roberto Ferrara et al.

JOURNAL OF THORACIC ONCOLOGY (2018)

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Review Pharmacology & Pharmacy

Role of RET protein-tyrosine kinase inhibitors in the treatment RET-driven thyroid and lung cancers

Robert Roskoski et al.

PHARMACOLOGICAL RESEARCH (2018)

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Article Oncology

Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC): Outcomes with immune check-point inhibitors (ICPi)

Elizabeth Dudnik et al.

LUNG CANCER (2018)

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Article Oncology

Clinical outcomes with pemetrexed-based systemic therapies in RET-rearranged lung cancers

A. Drilon et al.

ANNALS OF ONCOLOGY (2016)

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Article Oncology

Sorafenib treatment for patients with RET fusion-positive non-small cell lung cancer

Atsushi Horiike et al.

LUNG CANCER (2016)

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Article Oncology

Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway

Chen Lin et al.

ONCOTARGET (2016)

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