Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report

Pizzutilo, Elio Gregory; Agostara, Alberto G.; Roazzi, Laura; Romanò, Rebecca; Motta, Valentina; Lauricella, Calogero; Marrapese, Giovanna; Cerea, Giulio; Signorelli, Diego; Veronese, Silvio; Giannetta, Laura; Siena, Salvatore

doi:10.1016/j.jtocrr.2023.100555

Cited by 3 publications

(1 citation statement)

References 3 publications

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“…ROS1 G2032R and MET amplifications are the most common on-target and off-target alterations associated with resistance to ROS1 inhibitors. Recent studies have identified the ROS1 F2004V mutation, which can still be inhibited by repotrectinib [120]. Zhao et al identified through molecular dynamics simulations that patients with the ROS1 L2010M mutation may exhibit resistance to lorlatinib, entrectinib, cabozantinib, and crizotinib, while those with the ROS1 G1957A mutation may show resistance to ceritinib and cabozantinib [118].…”

Section: Ros Proto-oncogene 1 (Ros1)mentioning

confidence: 99%

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

Li,

Gong,

Zhou

et al. 2024

IJMS

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Over 120 small-molecule kinase inhibitors (SMKIs) have been approved worldwide for treating various diseases, with nearly 70 FDA approvals specifically for cancer treatment, focusing on targets like the epidermal growth factor receptor (EGFR) family. Kinase-targeted strategies encompass monoclonal antibodies and their derivatives, such as nanobodies and peptides, along with innovative approaches like the use of kinase degraders and protein kinase interaction inhibitors, which have recently demonstrated clinical progress and potential in overcoming resistance. Nevertheless, kinase-targeted strategies encounter significant hurdles, including drug resistance, which greatly impacts the clinical benefits for cancer patients, as well as concerning toxicity when combined with immunotherapy, which restricts the full utilization of current treatment modalities. Despite these challenges, the development of kinase inhibitors remains highly promising. The extensively studied tyrosine kinase family has 70% of its targets in various stages of development, while 30% of the kinase family remains inadequately explored. Computational technologies play a vital role in accelerating the development of novel kinase inhibitors and repurposing existing drugs. Recent FDA-approved SMKIs underscore the importance of blood–brain barrier permeability for long-term patient benefits. This review provides a comprehensive summary of recent FDA-approved SMKIs based on their mechanisms of action and targets. We summarize the latest developments in potential new targets and explore emerging kinase inhibition strategies from a clinical perspective. Lastly, we outline current obstacles and future prospects in kinase inhibition.

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Section: Ros Proto-oncogene 1 (Ros1)mentioning

confidence: 99%

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

Li,

Gong,

Zhou

et al. 2024

IJMS

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Repotrectinib: First Approval

Dhillon

2024

Drugs

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A next-generation, oral, small-molecule kinase inhibitor is being developed by Turning Point Therapeutics (a subsidiary of BMS) the treatment of locally advanced or metastatic solid tumours, including NSCLC • Received its first approval on 15 November 2023 in the USA • Approved for the treatment of adults with locally advanced or metastatic ROS1-positive NSCLC This summary represents the opinions of the [author/authors]. For a full list of declarations, including funding and author disclosure statements, and copyright information, please see the full text online.

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Analysis of CD74 Occurrence in Oncogenic Fusion Proteins

Vargas,

Pantouris

2023

IJMS

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CD74 is a type II cell surface receptor found to be highly expressed in several hematological and solid cancers, due to its ability to activate pathways associated with tumor cell survival and proliferation. Over the past 16 years, CD74 has emerged as a commonly detected fusion partner in multiple oncogenic fusion proteins. Studies have found CD74 fusion proteins in a range of cancers, including lung adenocarcinoma, inflammatory breast cancer, and pediatric acute lymphoblastic leukemia. To date, there are five known CD74 fusion proteins, CD74-ROS1, CD74-NTRK1, CD74-NRG1, CD74-NRG2α, and CD74-PDGFRB, with a total of 16 different variants, each with unique genetic signatures. Importantly, the occurrence of CD74 in the formation of fusion proteins has not been well explored despite the fact that ROS1 and NRG1 families utilize CD74 as the primary partner for the formation of oncogenic fusions. Fusion proteins known to be oncogenic drivers, including those of CD74, are typically detected and targeted after standard chemotherapeutic plans fail and the disease relapses. The analysis reported herein provides insights into the early intervention of CD74 fusions and highlights the need for improved routine assessment methods so that targeted therapies can be applied while they are most effective.

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Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report

Cited by 3 publications

References 3 publications

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

Repotrectinib: First Approval

Analysis of CD74 Occurrence in Oncogenic Fusion Proteins

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