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首页> 外文期刊>Pulmonary therapy. >Molecular Bases for Combinatorial Treatment Strategies in Patients with KRAS Mutant Lung Adenocarcinoma and Squamous Cell Lung Carcinoma
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Molecular Bases for Combinatorial Treatment Strategies in Patients with KRAS Mutant Lung Adenocarcinoma and Squamous Cell Lung Carcinoma

机译：KRAS突变型肺腺癌和鳞状细胞肺癌患者联合治疗策略的分子基础

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Innovative therapeutic agents have significantly improved outcomes, with an acceptable safety profile, in a substantial proportion of non-small cell lung cancer (NSCLC) patients in whom the malignant phenotype of the disease is determined by oncogenic molecular alterations. However, the benefit seen with these treatment models has not translated well to NSCLCs with KRAS mutations or squamous cell histology. Although efforts have been made to develop precision medicine approaches, KRAS mutant NSCLC and lung squamous cell carcinoma (LSCC) continue to display resistance to therapy. Recently, based on the results of the Phase III SQUIRE trial, the EGFR monoclonal antibody necitumumab received FDA authorization in combination with cisplatin and gemcitabine for first line treatment of patients with metastatic LSCC. Among the molecular compounds tested in KRAS mutant NSCLC patients, the MEK inhibitor, selumentinib, combined with docetaxel in second line setting, determined a progression-free survival improvement, but no overall survival advantage. Better understanding is needed in regard to signaling pathways which cooperate to induce oncogene transformation in LSCC and KRAS mutant NSCLC and could determine intrinsic or acquired resistance to necitumumab and selumetinib. Greater understanding of such pathways will provide a molecular base upon which to improve the scant clinical benefit with these compounds.
机译：在相当大比例的非小细胞肺癌（NSCLC）患者中，创新性治疗药物具有显着改善的结果，并具有可接受的安全性，在这些患者中，该疾病的恶性表型由致癌分子改变决定。然而，这些治疗模型所见的益处尚未很好地转化为具有KRAS突变或鳞状细胞组织学的NSCLC。尽管已努力开发精密医学方法，但KRAS突变型NSCLC和肺鳞状细胞癌（LSCC）继续显示出对治疗的抵抗力。最近，基于III期SQUIRE试验的结果，EGFR单克隆抗体necitumumab已获得FDA的授权与顺铂和吉西他滨联合用于转移性LSCC患者的一线治疗。在KRAS突变型NSCLC患者中测试的分子化合物中，MEK抑制剂selumentinib与多西他赛联合用于二线治疗，确定了无进展生存改善，但没有总体生存优势。关于信号传导途径需要更好的理解，这些信号传导途径协同诱导LSCC和KRAS突变NSCLC中的癌基因转化，并可能确定对necitumumab和selumetinib的内在或获得性耐药。对此类途径的更深入了解将提供分子基础，以改善这些化合物的临床价值。

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