Targeting the Tumor Environment in Squamous Cell Carcinoma of the Head and Neck.
The survival rate for patients with advanced stages of squamous cell carcinoma of the head and neck (SCCHN) remains poor despite multimodal treatment options. Cetuximab, an anti-EGFR inhibitor, is the only FDA-approved targeted agent for this disease. Recent findings have implicated modifications of the microenvironment and, consequently, phenotypical modifications of the cancer cell, in treatment resistance mechanisms. For many years, cancer research has focused mainly on targetable sites on or inside the cancer cell. Nowadays, in preclinical and clinical studies, a greater emphasis is being placed on drugs that target the tumor microenvironment. Potential targets relate to tumor vascularization, immunology, extracellular matrix components, or cancer-associated fibroblasts. The combination of these new agents with standard treatment options is of particular interest to overcome resistance mechanisms and/or to increase treatment efficacy. Whereas antiangiogenic agents show poor clinical activity, immunotherapy seems to be a more promising tool with an objective response rate (ORR) of 20 % in patients with recurrent and/or metastatic squamous cell carcinoma (R/M SCC). Other targets, located inside the extracellular matrix or on cancer associated fibroblasts, are under preclinical investigation. These new agents all need to be tested in clinical trials alone, or in combination with standard treatment modalities, based on preclinical data. To increase our knowledge of the complex network between the cancer cell and its environment, preclinical studies should consider co-culture models, and clinical studies should incorporate a translational research objective.
Institut Roi Albert II, Department of Head and Neck Surgery, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (MIRO), Université Catholique de Louvain, Avenue Hippocrate, 1200, Brussels, Belgium. sandra.schmitz@uclouvain.be.
Sandra
S
Schmitz
Institut Roi Albert II, Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (MIRO), Université Catholique de Louvain, Avenue Hippocrate, 1200, Brussels, Belgium.
Jean-Pascal
JP
Machiels
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D000072645:Cancer-Associated Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000473:pathology* / Q000628:therapy*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000209:etiology* / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
Angiogenesis; Cancer associated fibroblasts; Clinical data; Extracellular matrix; Head and neck cancer; Immunology; New treatment options; Preclinical data; Squamous cell carcinoma