Egfr Antibody
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2021 ◽  
Vol 12 ◽  
Hasan Baysal ◽  
Ines De Pauw ◽  
Hannah Zaryouh ◽  
Marc Peeters ◽  
Jan Baptist Vermorken ◽  

Cetuximab has an established role in the treatment of patients with recurrent/metastatic colorectal cancer and head and neck squamous cell cancer (HNSCC). However, the long-term effectiveness of cetuximab has been limited by the development of acquired resistance, leading to tumor relapse. By contrast, immunotherapies can elicit long-term tumor regression, but the overall response rates are much more limited. In addition to epidermal growth factor (EGFR) inhibition, cetuximab can activate natural killer (NK) cells to induce antibody-dependent cellular cytotoxicity (ADCC). In view of the above, there is an unmet need for the majority of patients that are treated with both monotherapy cetuximab and immunotherapy. Accumulated evidence from (pre-)clinical studies suggests that targeted therapies can have synergistic antitumor effects through combination with immunotherapy. However, further optimizations, aimed towards illuminating the multifaceted interplay, are required to avoid toxicity and to achieve better therapeutic effectiveness. The current review summarizes existing (pre-)clinical evidence to provide a rationale supporting the use of combined cetuximab and immunotherapy approaches in patients with different types of cancer.

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1045
Morena Fasano ◽  
Francesco Perri ◽  
Carminia Maria Della Corte ◽  
Raimondo Di Liello ◽  
Giuseppina Della Vittoria Scarpati ◽  

Head and neck squamous cell carcinoma (HNSCC) is characterized by a high mortality rate owing to very few available oncological treatments. For many years, a combination of platinum-based chemotherapy and anti-EGFR antibody cetuximab has represented the only available option for first-line therapy. Recently, immunotherapy has been presented an alternative for positive PD-L1 HNSCC. However, the oncologists’ community foresees that a new therapeutic era is approaching. In fact, no-chemo options and some molecular targets are on the horizon. This narrative review addresses past, present, and future therapeutic options for HNSCC from a translational point of view.

Hui K Gan ◽  
Sagun Parakh ◽  
Andrew B Lassman ◽  
Aidan Seow ◽  
Eddie Lau ◽  

Abstract Background The adverse impact of increasing brain tumor size on the efficacy of antibody drug conjugates (ADCs) was investigated preclinically then validated with clinical data. Methods Preclinical study: The impact of tumor size on ADC tumor delivery and treatment response was evaluated in an EGFR-amplified patient derived glioblastoma (GBM) model following treatment with Depatuxizumab mafadotin (Depatux-M). Biodistribution and imaging studies correlated drug distribution with starting treatment volume and anti-tumor activity. Clinical study: M12-356 was a Phase I study of Depatux-M in patients with GBM. Blinded volumetric analysis of baseline tumor volumes of M12-356 patients was undertaken by two reviewers and results correlated with response and survival. Results Preclinically, imaging and biodistribution studies showed specific and significantly higher tumor uptake of zirconium-89 labeled Depatux-M ( 89Zr-Depatux-M) in mice with smaller tumor volume (~98mm 3) versus those with larger volumes (~365mm 3); concordantly, mice with tumor volumes ≤100mm 3 at treatment commencement had significantly better growth inhibition by Depatux-M (93% vs 27%, p<0.001) and significantly longer overall survival (p<0.0001) compared to tumors ≥400mm 3. Clinically, patients with tumor volumes < 25cm 3 had significantly higher response rates (17% vs. 0%, p=0.009) and longer overall survival (0.5 vs 0.89 years, p=0.001) than tumors above 25 cm 3. Conclusion Both preclinical and clinical data showed intra-tumoral concentration and efficacy of Depatux-m inversely correlated with tumor size. This finding merit further investigation with pre-treatment tumor volume as a predictor for response to ADCs, in both gliomas and other solid tumors.

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3544
Han-Hsing Tsou ◽  
Hong-Chieh Tsai ◽  
Chiao-Ting Chu ◽  
Hsiao-Wei Cheng ◽  
Chung-Ji Liu ◽  

Oral squamous cell carcinoma (OSCC) accounts for 80–90% of all intraoral malignant neoplasms. The single greatest risk factor for oral cancer is tobacco use, including cigarettes, cigars, chewing tobacco, and snuff. Aberrations of the epidermal growth factor receptor (EGFR) pathway features prominently in oral tumorigenesis and progression. It was shown that cigarette smoking (CS) is associated with worse prognosis in OSCC patients and overexpression of EGFR in tumor tissue. However, the mechanism by which cigarette smoking induced EGFR pathway activation remains to be fully elucidated. Acrolein, an IARC group 2A carcinogen, is a highly reactive aldehyde found in CS. Here we report that acrolein is capable of inducing tumorigenic transformation in normal human oral keratinocytes (NOK). The acrolein-transformed NOK cells showed EGFR copy number amplification, increased EGFR expression, and activation of downstream ERK and AKT signaling pathway. No p53 mutations were observed in acrolein-transformed NOK cells. Inhibiting EGFR pathway using an anti-EGFR antibody, cetuximab, inhibits tumor growth. Furthermore, by examining tissue sample from patients, we found an increased EGFR copy number was positively associated with acrolein-induced DNA damages in OSCC patients. Taken together, our results indicate that acrolein is important in tumorigenic transformation through amplification of EGFR and activating the downstream signaling pathway, contributing to oral carcinogenesis. This is the first study to provide molecular evidence showing that CS containing acrolein contributes to EGFR amplification in OSCC.

2021 ◽  
Niklas Baumann ◽  
Thies Rösner ◽  
J. H. Marco Jansen ◽  
Chilam Chan ◽  
Klara Marie Eichholz ◽  

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