Effects of PHA-665752 and Cetuximab Combination Treatment on In Vitro and Murine Xenograft Growth of Human Colorectal Cancer Cells with KRAS or BRAF Mutations

Jia, Yitao; Yang, Dongyuan; Zhao, Zhaolong; Bi, Xin; Han, Wei; Feng, Bo; Zhi, Jie; Gu, Bin; Duan, Zhihui; Wu, Jianhua; Ju, Yingchao; Wang, Mingxia; Li, Zhongxin

doi:10.2174/1568009617666170330112841

Cited by 4 publications

(2 citation statements)

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“…The proportion of infiltrating lymphocytes in tumor tissues increased or decreased significantly during the course of treatment even during the use of immunoregulatory drug for therapy [131]. In mouse models of highly aggressive mesenchymal CRC tumors, a potential synergistic effect was observed with the combination of a TGFR inhibitor with a PD-1 checkpoint inhibitor [133], or with an agonistic OX40 mAb [134], which enhanced effector function and survival of activated T cells. The positive treatment outcome was associated with an expansion of tumor-infiltrating effector CTLs and TH1 cells, enhanced antitumor T-cell immunity [135], and a high tumor-specific IFN-γ response [136].…”

Section: Strategy To Overcome the Acquire Immune Resistance In Crc Re...mentioning

confidence: 99%

Strategy to targeting the immune resistance and novel therapy in colorectal cancer

Wang

Guan

et al. 2018

Cancer Medicine

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Assessing the CRC subtypes that can predict the outcome of colorectal cancer (CRC) in patients with immunogenicity seems to be a promising strategy to develop new drugs that target the antitumoral immune response. In particular, the disinhibition of the antitumoral T‐cell response by immune checkpoint blockade has shown remarkable therapeutic promise for patients with mismatch repair (MMR) deficient CRC. In this review, the authors provide the update of the molecular features and immunogenicity of CRC, discuss the role of possible predictive biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the most relevant ongoing preclinical study and clinical trials such as the use of the combination therapy with immunotherapy. Furthermore, this work is further to understand the complex interactions between the immune surveillance and develop resistance in tumor cells. As expected, if the promise of these developments is fulfilled, it could develop the effective therapeutic strategies and novel combinations to overcome immune resistance and enhance effector responses, which guide clinicians toward a more “personalized” treatment for advanced CRC patients.

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Section: Strategy To Overcome the Acquire Immune Resistance In Crc Re...mentioning

confidence: 99%

Strategy to targeting the immune resistance and novel therapy in colorectal cancer

Wang

Guan

et al. 2018

Cancer Medicine

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“…Small molecule c-Met kinase inhibitors target activation sites of the receptor inside the cells via inhibiting phosphorylation and its downstream signaling pathway. PHA-665752, c-Met inhibitor, with the combination of cetuximab suppressed more efficiently the CRC cell growth in vitro and in vivo compared with either single agent treatment ( 129 ). In addition, miRNA, such as miR-206, has been identified to be able to affect the c-MET/HGF signaling pathway via inhibiting CRC cells proliferation and invasion ( 130 ).…”

Section: Opportunities For Crc Treatmentmentioning

confidence: 99%

Molecular Network of Colorectal Cancer and Current Therapeutic Options

Huang

Yang

2022

Front. Oncol.

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Colorectal cancer (CRC), a leading cause of cancer-related mortalities globally, results from the accumulation of multiple genetic and epigenetic alterations in the normal colonic and rectum epithelium, leading to the progression from colorectal adenomas to invasive carcinomas. Almost half of CRC patients will develop metastases in the course of the disease and most patients with metastatic CRC are incurable. Particularly, the 5-year survival rate of patients with stage 4 CRC at diagnosis is less than 10%. Although genetic understanding of these CRC tumors and paired metastases has led to major advances in elucidating early driver genes responsible for carcinogenesis and metastasis, the pathophysiological contribution of transcriptional and epigenetic aberrations in this malignancy which influence many central signaling pathways have attracted attention recently. Therefore, treatments that could affect several different molecular pathways may have pivotal implications for their efficacy. In this review, we summarize our current knowledge on the molecular network of CRC, including cellular signaling pathways, CRC microenvironment modulation, epigenetic changes, and CRC biomarkers for diagnosis and predictive/prognostic use. We also provide an overview of opportunities for the treatment and prevention strategies in this field.

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Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer

Moosavi

Giovannetti

Peters

et al. 2021

Critical Reviews in Oncology/Hematology

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Effects of PHA-665752 and Cetuximab Combination Treatment on In Vitro and Murine Xenograft Growth of Human Colorectal Cancer Cells with KRAS or BRAF Mutations

Abstract: Combination treatment with PHA-665752 and cetuximab suppressed in vitro and in vivo CRC cell growth more than treatment with either agent alone did.

Cited by 4 publications

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Strategy to targeting the immune resistance and novel therapy in colorectal cancer

Strategy to targeting the immune resistance and novel therapy in colorectal cancer

Molecular Network of Colorectal Cancer and Current Therapeutic Options

Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer

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