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

Horiike, Atsushi; Takeuchi, Kengo; Uenami, Takeshi; Kawano, Yuko; Tanimoto, Azusa; Kaburaki, Kyohei; Tambo, Yuichi; Kudo, Kazuhiko; Yanagitani, Noriko; Ohyanagi, Fumiyoshi; Motoi, Noriko; Ishikawa, Yuichi; Horai, Takeshi; Nishio, Makoto

doi:10.1016/j.lungcan.2015.12.011

Cited by 50 publications

(38 citation statements)

References 19 publications

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“…11 In retrospective studies, two of 10 patients (22%) with RET-rearranged NSCLC treated with sunitinib experienced a PR, as opposed to none of five patients with RET-rearranged NSCLC treated with sorafenib. 49,78 A phase II clinical trial of sunitinib is ongoing in never-smokers with adenocarcinoma tumors not harboring EGFR, KRAS, or ALK molecular alterations (NCT01829217).…”

Section: Lenvatinibmentioning

confidence: 99%

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

Ferrara

Auger

Auclin

et al. 2018

Journal of Thoracic Oncology

176

151

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Since the discovery in 2012 of rearranged during transfection proto-oncogene gene (RET) rearrangements in NSCLC, at least 12 different fusion variants have been identified, with kinesin family member 5B gene (KIF5B)-RET being the most frequent and the best characterized. Unlike ALK receptor tyrosine kinase gene (ALK) and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry (IHC), although fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histologic subtype, never-smoking status, younger age, more advanced disease stage, potentially higher chemosensitivity (in particular, to pemetrexed-based regimens), and coexistence of other genomic alterations. To date, several preclinical models, clinical trials, and retrospective studies have investigated multitarget inhibitors with anti-rearranged during transfection proto-oncogene (RET) activity in patients with RET-rearranged lung cancer. In the clinical setting, the benefit in terms of response (16%-47%) and progression-free survival (2-7 months) is clearly not comparable to that seen with other targeted agents in oncogene-addicted NSCLC. Furthermore, multikinase agents showed high rates of severe toxicities, leading to frequent dose reduction and drug discontinuation. To date, no definitive conclusions about a potentially different impact of anti-RET therapies according to RET fusion variants have been drawn on account of discordant data coming mostly from small subgroup analyses. Importantly, the absence of a striking clinical benefit in RET oncogene-addicted NSCLC underscores the clear need for development of more selective and potent RET inhibitors and for better characterization of concomitant genomic alterations and mechanisms of resistance to RET inhibition in patients with lung cancer.

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Section: Lenvatinibmentioning

confidence: 99%

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

Ferrara

Auger

Auclin

et al. 2018

Journal of Thoracic Oncology

176

151

View full text Add to dashboard Cite

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“…RET inhibitors have had moderate success in a small number of patients with PTC or lung adenocarcinoma, having shown considerable toxicity (Borrello et al, 2013; Horiike et al, 2016; Xing et al, 2013). Thus, therapeutics for PTC remain a significant unmet need.…”

Section: Introductionmentioning

confidence: 99%

Drosophila Cancer Models Identify Functional Differences between Ret Fusions

Levinson

Cagan

2016

Cell Reports

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Summary We generated and compared Drosophila models of RET fusions CCDC6-RET and NCOA4-RET. Both RET fusions directed cells to migrate, delaminate, and undergo EMT, and both resulted in lethality when broadly expressed. In all phenotypes examined NCOA4-RET was more severe than CCDC6-RET, mirroring their effects on patients. A functional screen against the Drosophila kinome and against a library of cancer drugs found that CCDC6-RET and NCOA4-RET acted through different signaling networks and displayed distinct drug sensitivities. Combining data from the kinome and drug screens identified the WEE1 inhibitor AZD1775 plus the multi-kinase inhibitor sorafenib as a synergistic drug combination that is specific for NCOA4-RET. Our work emphasizes the importance of identifying and tailoring a patient’s treatment to their specific RET fusion isoform and identifies a multi-targeted therapy that may prove effective against tumors containing the NCOA4-RET fusion.

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“…Since, sorafenib did not show dramatic results, the study suggesting for testing of other RET inhibitors in the treatment of RET fusion-positive NSCLC [74]. • Sunitinib, is a RET tyrosine kinase inhibitor, and preclinical data of sunitinib suggest that it can play an important role in the clinical development of NSCLC treatment [74,75]. • Cabozantinib, in patients with RET fusion-positive NSCLC cancer, provides new drug treatment paradigm in lung cancers.…”

Section: Interventions For the Ret Mutationsmentioning

confidence: 99%

A Review: Status of Genetic Modulated Nonsmall Cell Lung Cancer Targets and Treatment (Current Updates in Drugs for Non-Small Cell Lung Cancer Treatment)

Kumar

Purohit

Dagar

2018

Asian J Pharm Clin Res

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Genetic modifications or mutations has been a bottleneck for the treatment of cancer; it is widely known to play a vital role in the progression of metastatic level/stage within the nonsmall cell lung cancer (NSCLC). The NSCLC of cancer is responsible for lung cancer lawsuits. In the various genetic mutations related study has been concluded with the various genes findings, which are named as the epidermal growth factor receptor, anaplastic lymphoma kinase, Kristen rat sarcoma virus, ROS proto-oncogene 1, human epidermal growth factor, B-RAF proto-oncogene, rearranged during Transfection, MET, Phosphatidyl 3-kinases CA, IGF-1R, NTRK1, FGFR1, and DDR2. The various research data supported this study. The involvement of the gene in the NSCLC patients made a paradigm shift in the drug discovery. The presence of one mutation in connection with some other could have an impact on NSCLC remedy.Utilizing this genotype-directed therapy for an advanced NSCLC has to turn out to be an appealing and efficacious treatment strategy. Here in the advancement of research, related genetic modulated targets and treatment have been discussed, particular genetic mutations help to find new updated interventions or medicinal drugs for the treatment of NSCLC. In there view, we have comprehensively arranged the mutation type and treatment with the status of NSCLC.

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

Cited by 50 publications

References 19 publications

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

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

Drosophila Cancer Models Identify Functional Differences between Ret Fusions

A Review: Status of Genetic Modulated Nonsmall Cell Lung Cancer Targets and Treatment (Current Updates in Drugs for Non-Small Cell Lung Cancer Treatment)

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