Targeting the ERBB family in cancer: couples therapy

Tebbutt, Niall C.; Pedersen, Mikkel Wandahl; Johns, Terrance G.

doi:10.1038/nrc3559

Cited by 384 publications

(353 citation statements)

References 86 publications

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“…EGFR TKIs directly bind to the kinase domain and block its kinase activity, including the first-generation EGFR TKIs Erlotinib and Gefitinib, second-generation Aftinib and third-generation AZD9191. Conversely, EGFR-targeting antibodies such as Cetuximab, Panitumumab and nimotuzumab bind extracellularly, blocking ligand binding and preventing receptor dimerization (15).…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity of nimotuzumab in combination with cisplatin in lung cancer cell line A549 inï¿½vitro

Yang

Zhou

et al. 2018

Oncol Lett

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Abstract. Nimotuzumab, a humanized IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR), increases radiosensitivity in lung cancer. Cisplatin is an effective antitumor agent in lung cancer. In the present study, the antitumor activity of nimotuzumab combined with cisplatin was investigated in A549 lung cancer cells. Viability, cell cycle distribution and cyclin D1 expression were assessed following treatment with nimotuzumab alone, cisplatin alone, nimotuzumab in combination with cisplatin, and nimotuzumab followed sequentially by cisplatin. The inhibitory effect on cell viability of nimotuzumab sequentially followed by cisplatin was higher compared with cisplatin alone (82.17±1.62 vs. 56.97±1.42%). Compared with treatment by cisplatin alone, cell cycle analysis by flow cytometry demonstrated that the percentage of cells in the G 0 /G 1 phase was increased when A549 cells were treated with nimotuzumab followed sequentially by cisplatin (P<0.01). However, the proportion of cells in G 0 /G 1 phase was decreased when A549 cells were treated with nimotuzumab and cisplatin simultaneously compared with cisplatin alone (P<0.05). Cyclin D1 expression was decreased in all chemotherapy treatment groups; the most significant decrease was in A549 cells treated with nimotuzumab followed sequentially by cisplatin. Nimotuzumab may enhance the antitumor activity of cisplatin on A549 cells. The cell cycle arrest at G 0 /G 1 observed may have been due to decreased cyclin D1 levels. Potential antagonism was identified when A549 cells were treated with nimotuzumab and cisplatin simultaneously, indicating that targeted therapy may be more effective when administered prior to conventional chemotherapy. IntroductionLung cancer has been the most common cancer worldwide, and the leading cause of cancer-associated mortality, since 1985 (1). The 5-year survival rate for lung carcinoma overall is poor, at 16-17% (2). Surgery is not suitable for the majority of patients with lung cancer, as diagnoses are often obtained at advanced disease stages. The standard of care for advanced non-small cell lung cancer (NSCLC) is cisplatin in combination with 1 to 3 of the following drugs: Paclitaxel, gemcitabine and docetaxel (3). The efficacy of chemotherapy is limited due to its side effects and the lack of response in certain sub-populations of patients. Research efforts have focused on identifying molecular targets and developing molecular-targeted therapies based on the understanding of the molecular abnormalities associated with lung cancer (4-6).Insight into the pathobiology of NSCLC has facilitated the development of targeted molecular therapies that target specific mutations that serve critical roles in the progression to aggressive disease. Mutations in the epidermal growth factor receptor (EGFR), KRAS and anaplastic lymphoma kinase (ALK) genes are mutually exclusive in patients with NSCLC, and targeted therapy may be affected due to the existence of one mutation in lieu of another. Therefore, the detection of these mutati...

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Section: Introductionmentioning

confidence: 99%

Antitumor activity of nimotuzumab in combination with cisplatin in lung cancer cell line A549 inï¿½vitro

Yang

Zhou

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…In this work, the B7.1-IgV-like domain was used instead of anti-CD3 Ab due to its advantageous. It can direct CD28 cytotoxic T cells to kill tumor cells compared with the accessory cell-mediated killers such as macrophages, natural killer cells (NKC), and dendritic cells (DC) [5][6][7][8].…”

Section: V-d-j-regionmentioning

confidence: 99%

“…In the absence of a known ligand, hetero-dimerization of this receptor with other family members, particularly with EGFR which results in effective activation of intracellular signaling pathways, promotes cell proliferation and survival [3][4][5]. Since these cell surface receptors (HER2 and EGFR) are amplified and over-expressed in a large number of tumor types, they are considered as ideal targets for selective molecular therapy of cancer [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…Monoclonal antibodies' (mAbs) development against the extra-cellular domain of these receptors is an approach which is, currently, being taken to prevent their signaling. In recent years, various antibodies including humanized, chimeric, and more recently single-domain mAbs have been successfully developed against these receptors [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…Since these cell surface receptors (HER2 and EGFR) are amplified and over-expressed in a large number of tumor types, they are considered as ideal targets for selective molecular therapy of cancer [1][2][3][4][5]. Monoclonal antibodies' (mAbs) development against the extra-cellular domain of these receptors is an approach which is, currently, being taken to prevent their signaling.…”

Section: Introductionmentioning

confidence: 99%

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