Capmatinib and paclitaxel combination: a novel strategy for overcoming challenges in triple-negative breast cancer treatment.

Authors

Ahmad Habibian Sezavar, Fatemeh Fakhari, Emad Jafarzadeh, Vahideh Montazeri, Amir Shadborestan, Mohammad Abdollahi, Omid Sabzevari, Abbas Kebriaeizadeh, Ruhollah Hosseini, Shima Aliebrahimi, Seyed Nasser Ostad

Published in

BMC cancer. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with limited treatment options. Paclitaxel (PTX) is commonly used, but its effectiveness is hampered by resistance and metastasis. The c-Met receptor, which is often upregulated in TNBC, promotes tumor progression via the HGF/c-Met axis and downstream PI3K/AKT and MAPK pathways. This study explored whether Capmatinib (CAP), a selective c-Met inhibitor, can enhance PTX efficacy in TNBC.
MDA-MB-231 and 4T1 TNBC cell lines were treated with PTX and CAP, alone and in combination. Cytotoxicity, apoptosis, and cell cycle effects were assessed via MTT assays and flow cytometry. Cell migration was evaluated via scratch assays. The expression of epithelial-mesenchymal transition (EMT) markers (E-cadherin, vimentin, and Snail) was measured via real-time PCR. In vivo studies in BALB/c mice have evaluated hematological parameters, poor prognostic gene expression (BCL11, FOXC1, FOXM1), histopathology, and survival.
In MDA-MB-231 cells, combination therapy increased PTX cytotoxicity, induced G2/M arrest, increased apoptosis, and suppressed migration. Co-treatment upregulated E-cadherin and downregulated vimentin and Snail. A weak synergistic effect was observed in 4T1 cells. In vivo, co-treatment improved hematological indices, reduced the expression of genes related to poor prognosis, inhibited angiogenesis and necrosis, increased lymphocyte infiltration, and prolonged survival.
CAP enhances the antitumor activity of PTX in TNBC by targeting c-Met-mediated pathways. This combination therapy shows potential to overcome resistance and improve treatment outcomes in TNBC.

PMID:
42443810
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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