A single-arm phase II clinical trial of anlotinib combined with chemotherapy for the treatment of metastatic triple-negative breast cancer

Huang, Jiayi; Xie, Xiao-Feng; Chen, Xuelian; Zhang, Qiuyi; Chen, Liping; Bai, Xue; Lan, Xiao-Feng; Song, Lin; Guo, Jinfeng; Du, Chenxing

doi:10.3389/fonc.2023.1122294

Cited by 4 publications

(2 citation statements)

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“…A phase Ib clinical study showed that a combination of a tyrosine kinase inhibitor (anlotinib) and an immune checkpoint inhibitor (anti-PD-L1 antibody) showed promising efficacy with a good safety profile provides a chemotherapy-free treatment for TNBC patients 9 . In another phase II clinical trial, the combination of this tyrosine kinase inhibitor and chemotherapy also showed a certain efficacy and acceptable safety profile to treat metastatic triple-negative breast cancer patients 10 . A tyrosine kinase, SRC overexpression is frequently found in TNBC patients and associated with tumor malignancy.…”

Section: Discussionmentioning

confidence: 99%

N-phenyl pyrazoline derivative inhibits cell aggressiveness and enhances paclitaxel sensitivity of triple negative breast cancer cells

Satriyo,

Mustofa,

Wahyuningsih

et al. 2024

Sci Rep

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Protein kinase dysregulation induces cancer cell aggressiveness leading to rapid tumor progression and poor prognosis in TNBC patients. Many small-molecule kinase inhibitors have been tested in clinical trials to treat TNBC patients. In the previous study, we found that N-phenylpyrazoline small molecule acts as a protein kinase inhibitor in cervical cancer cells. However, there remains unknown about N-phenyl pyrazoline potency as a kinase inhibitor and its anti-cancer activity in TNBC cells. In this study, we investigated the activity of N-phenyl pyrazoline against TNBC cells via tyrosine kinase inhibition. Based on the MTT assay, the IC50 values for the N-phenyl pyrazoline 2, 5, A, B, C, and D against Hs578T were 12.63 µM, 3.95 µM, not available, 18.62 µM, 30.13 µM, and 26.79 µM, respectively. While only P5 exhibited the IC50 against MDA MB 231 (21.55 µM). Further, N-phenyl pyrazoline 5 treatment significantly inhibited the cell proliferation rate of Hs578T and MDA MB 231 cells. The migration assay showed that treatment with the compound N-phenyl pyrazoline 5 with 4 µM concentration significantly reduced cell migration of Hs578T cells. N-phenyl pyrazoline 5 treatment at 1 µM and 2 µM was able to reduce the tumorsphere size of Hs578t cells. A combination treatment of P5 and paclitaxel showed a synergistic effect with a combination index score > 1 in both TNBC cells. Further, the P5 predictively targeted the protein kinases that significantly correlated to breast cancer prognosis. The GSEA analysis result shows that receptor tyrosine kinase, Notch3, Notch4, and Ephrin signaling pathways were targeted by P5. The P5 treatment reduced the EGFR expression level and activation in TNBC cells.

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Section: Discussionmentioning

confidence: 99%

N-phenyl pyrazoline derivative inhibits cell aggressiveness and enhances paclitaxel sensitivity of triple negative breast cancer cells

Satriyo,

Mustofa,

Wahyuningsih

et al. 2024

Sci Rep

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“…This combination not only demonstrated favorable efficacy but also maintained a manageable safety profile ( 107 ). Another Phase II clinical trial combining Anlotinib with standard chemotherapy for metastatic TNBC demonstrated therapeutic benefits with manageable safety ( 108 ).…”

Section: Current Therapeutic Applications Of the Jak2/stat3 Signaling...mentioning

confidence: 99%

Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer

Long,

Fei,

Chen

et al. 2024

Front. Oncol.

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Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its propensity for metastasis and poor prognosis. TNBC evades the body’s immune system recognition and attack through various mechanisms, including the Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. This pathway, characterized by heightened activity in numerous solid tumors, exhibits pronounced activation in specific TNBC subtypes. Consequently, targeting the JAK2/STAT3 signaling pathway emerges as a promising and precise therapeutic strategy for TNBC. The signal transduction cascade of the JAK2/STAT3 pathway predominantly involves receptor tyrosine kinases, the tyrosine kinase JAK2, and the transcription factor STAT3. Ongoing preclinical studies and clinical research are actively investigating this pathway as a potential therapeutic target for TNBC treatment. This article comprehensively reviews preclinical and clinical investigations into TNBC treatment by targeting the JAK2/STAT3 signaling pathway using small molecule compounds. The review explores the role of the JAK2/STAT3 pathway in TNBC therapeutics, evaluating the benefits and limitations of active inhibitors and proteolysis-targeting chimeras in TNBC treatment. The aim is to facilitate the development of novel small-molecule compounds that target TNBC effectively. Ultimately, this work seeks to contribute to enhancing therapeutic efficacy for patients with TNBC.

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Developing combination therapies with biologics in triple-negative breast cancer

Gaudio,

Martino,

Pellizzari

et al. 2024

Expert Opinion on Biological Therapy

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A single-arm phase II clinical trial of anlotinib combined with chemotherapy for the treatment of metastatic triple-negative breast cancer

Cited by 4 publications

References 46 publications

N-phenyl pyrazoline derivative inhibits cell aggressiveness and enhances paclitaxel sensitivity of triple negative breast cancer cells

N-phenyl pyrazoline derivative inhibits cell aggressiveness and enhances paclitaxel sensitivity of triple negative breast cancer cells

Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer

Developing combination therapies with biologics in triple-negative breast cancer

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