<i>In vitro</i> combined treatment with cetuximab and trastuzumab inhibits growth of colon cancer cells

Luca, Tonia; Barresi, Vincenza; Privitera, Giovanna; Musso, Nicolò; Caruso, Massimo; Condorelli, D. F.; Castorina, Sergio

doi:10.1111/cpr.12125

Cited by 23 publications

(16 citation statements)

References 55 publications

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“…Among the proposed mechanism of action of this agent, ADCC is suggested as a major mechanism of trastuzumab-mediated tumor cell death [ 37 , 38 ]. Further, HCT116 cells have previously been reported to express HER2 receptor [ 39 ] and trastuzumab-mediated HER-2 inhibition failed to block HCT116 cell proliferation [ 40 ]. Therefore, HCT116-derived cells were exposed to trastuzumab and effector cells, and target cell death was evaluated.…”

Section: Resultsmentioning

confidence: 99%

miR-143 or miR-145 overexpression increases cetuximab-mediated antibody-dependent cellular cytotoxicity in human colon cancer cells

et al. 2016

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miR-143 and miR-145 are downregulated in colon cancer. Here, we tested the effect of restoring these miRNAs on sensitization to cetuximab in mutant KRAS (HCT116 and SW480) and wild-type KRAS (SW48) colon cancer cells. We evaluated cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) and the modulation of signaling pathways involved in immune effector cell-mediated elimination of cancer cells. Stable miR-143 or miR-145 overexpression increased cell sensitivity to cetuximab, resulting in a significant increase of cetuximab-mediated ADCC independently of KRAS status. Importantly, HCT116 cells overexpressing these miRNAs triggered apoptosis in result of cetuximab-mediated ADCC, effected by peripheral blood mononuclear cells (p < 0.01). This was associated with increased apoptosis and caspase-3/7 activity, and reduced Bcl-2 protein expression (p < 0.01). In addition, caspase inhibition abrogated cetuximab-mediated ADCC in HCT116 cells overexpressing either miR-143 or miR-145 (p < 0.01). Furthermore, Bcl-2 silencing led to high level of cetuximab-mediated ADCC, compared to control siRNA (p < 0.05). Importantly, granzyme B inhibition, abrogated cetuximab-mediated ADCC, reducing caspase-3/7 activity (p < 0.01). Collectively, our data suggests that re-introduction of miR-143 or miR-145 may provide a new approach for development of therapeutic strategies to re-sensitize colon cancer cells to cetuximab by stimulating cetuximab-dependent ADCC to induce cell death.

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Section: Resultsmentioning

confidence: 99%

miR-143 or miR-145 overexpression increases cetuximab-mediated antibody-dependent cellular cytotoxicity in human colon cancer cells

et al. 2016

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“…[117][118][119] Preclinical studies revealed that HER2 amplification might compensate for EGFR blockade, and combined targeting of HER2 and EGFR inhibited tumor cell proliferation, producing an effect that was stronger than that achieved using either single agent alone. 115,118,120 Several clinical trials have been developed to determine whether targeted agents against HER2positive CRC (determined by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), or chromogenic in situ hybridization) can be as effective as those against breast cancer or gastric cancer. A few of these studies using a single HER2-targeted agent, CRC colorectal cancer, mCRC metastatic colorectal cancer, PI3K phosphoinositide 3-kinase, AKT protein kinase B, also known as PKB, mTOR mammalian target of rapamycin, MEK mitogen-activated protein kinase, EGFR epidermal growth factor receptor, HER2/3/4 human epidermal growth factor 2/3/4, MAPK mitogenactivated protein kinase, STAT3 signal transducer and activator of transcription 3…”

Section: The Egfr-related Pathwaymentioning

confidence: 99%

Comprehensive review of targeted therapy for colorectal cancer

Xie

Chen

Fang

2020

Sig Transduct Target Ther

1,135

821

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Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents blocking different critical pathways as well as immune checkpoints are emerging at an unprecedented rate. Guidelines worldwide are currently updating the recommended targeted drugs on the basis of the increasing number of high-quality clinical trials. This review provides an overview of existing CRC-targeted agents and their underlying mechanisms, as well as a discussion of their limitations and future trends.

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“…When combined with the tyrosinekinase inhibitor gefitinib, the anti-tumor effect of cetuximab was augmented in colon cancer cell lines (59). The combination of cetuximab and trastuzumabled to inhibition of cell proliferation in colon cancer cells in a time-and dose-dependent manner and was associated with abnormal copy numbers of the EGFR gene (60). Cetuximab-conjugated gamma-poly (glutamic acid)-docetaxelnanomedicines induced cell death of HT-29 cells by enhancing cell cycle arrest in the G2/M phase compared to therapy without cetuximab conjugation (61).…”

Section: Cetuximab Efficacy and Resistance In Crc Treatment: Mechanismsmentioning

confidence: 99%

Epidermal growth factor receptor-targeted therapy in colorectal cancer

Jing

Zhang

2016

Front Biosci

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The epidermal growth factor receptor (EGFR) family plays an important role in colorectal cancer (CRC). EGFR participates in the key process of tumorigenesis and invasion, and its expression correlates with the prognosis of CRC. EGFR-targeted therapy has been widely utilized in stage III and IV CRC. The EGFR antibodies, cetuximab and panitumumab, are widely used in treatment of CRC. There are clinical trials and in vivo studies being carried out on the efficacy and mechanism of their action in CRC treatment. In this review, we will describe the EGFR-targeted therapy used in CRC, focusing on the efficacy and mechanisms of the most commonly used EGFR antibodies, cetuximab and panitumumab.

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In vitro combined treatment with cetuximab and trastuzumab inhibits growth of colon cancer cells

Abstract: Targeting EGFR and HER-2 simultaneously could have useful applications in colorectal cancer treatment. To improve pharmacological efficacy of cetuximab and trastuzumab combination, molecular mechanisms involved in their activity need to be elucidated.

Cited by 23 publications

References 55 publications

miR-143 or miR-145 overexpression increases cetuximab-mediated antibody-dependent cellular cytotoxicity in human colon cancer cells

miR-143 or miR-145 overexpression increases cetuximab-mediated antibody-dependent cellular cytotoxicity in human colon cancer cells

Comprehensive review of targeted therapy for colorectal cancer

Epidermal growth factor receptor-targeted therapy in colorectal cancer

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