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Drug Combinatorial Therapies for Treatment of KRAS Mutated Lung Cancers.

Hao He,Chang Xu,Zhao Cheng,Xiaoying Qian,Lei Zheng

Published 2019 in Current Topics in Medicinal Chemistry

ABSTRACT

KRAS is the most common oncogene to be mutated in lung cancer, and therapeutics directly targeting KRAS has proven to be challenging. The mutations of KRAS are associated with poor prognosis, resistance to both adjuvant therapy and targeted EGFR TKI. The EGFR TKI provide significant clinical benefit for patients whose tumors bear EGFR mutations. However, tumors with KRAS mutations rarely respond to EGFR TKI therapy. Thus, the combination therapy is essential for the treatment of lung cancers with KRAS mutations. EGFR TKI combined with inhibitors of MAPKs, PI3K/mTOR, HDAC, Wee1, PARP, CDK and Hsp90, even miRNAs and immunotherapy, were reviewed. Although the effects of the combination vary, the combined therapeutics are of the best options at present to treat KRAS mutated lung cancer.

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