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두경부 편평상피세포암에 대한 최근 약제 개발과 연구 방향

Current Development and Research Trend of Chemotherapeutic Agents for Head and Neck Squamous Cell Carcinoma

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초록

After FDA approval of cetuximab at 2006, receptor tyrosine kinase, including an epidermalgrowth factor receptor, blocking agents have been evaluated for head and neck squamous cellcarcinoma (HNSCC). Agents targeting PI3K/Akt/mTOR, IL-6/JAK/STAT3, vascular endothelialgrowth factor receptor, and cyclin D-CDK-4/6-INK4/Rb pathway have developed. Most ofthem have failed to demonstrate better treatment outcome in recurrent and/or metastatic (R/M)HNSCC than conventional chemotherapy. Since a pivotal role of PD-1/PD-L1 pathway in immunologicaltumor microenvironment was revealed, the immune checkpoint inhibitors, includingpembrolizumab and nivolumab, have opened new paradigm of cancer treatment modality andpropagates other immune-based therapies for R/M HNSCC. Various types of combination trialsconsisting of immunotherapy with other class of immunotherapy, targeted agents, radiationtherapy, or conventional chemotherapy have been under investigation to improve treatment outcome. Biomarker studies to find an optimal candidate for the newly developed agents are accompanied. These clinical trials lead to tailored approach based on immunotherapy with precisionmedicine is expected to lead to promising results.

Abstract

After FDA approval of cetuximab at 2006, receptor tyrosine kinase, including an epidermalgrowth factor receptor, blocking agents have been evaluated for head and neck squamous cellcarcinoma (HNSCC). Agents targeting PI3K/Akt/mTOR, IL-6/JAK/STAT3, vascular endothelialgrowth factor receptor, and cyclin D-CDK-4/6-INK4/Rb pathway have developed. Most ofthem have failed to demonstrate better treatment outcome in recurrent and/or metastatic (R/M)HNSCC than conventional chemotherapy. Since a pivotal role of PD-1/PD-L1 pathway in immunologicaltumor microenvironment was revealed, the immune checkpoint inhibitors, includingpembrolizumab and nivolumab, have opened new paradigm of cancer treatment modality andpropagates other immune-based therapies for R/M HNSCC. Various types of combination trialsconsisting of immunotherapy with other class of immunotherapy, targeted agents, radiationtherapy, or conventional chemotherapy have been under investigation to improve treatment outcome. Biomarker studies to find an optimal candidate for the newly developed agents are accompanied. These clinical trials lead to tailored approach based on immunotherapy with precisionmedicine is expected to lead to promising results.

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