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Published on: December 1, 2016
Drug Combinatorial Therapies for the Treatment of KRAS Mutated Lung Cancers
Hao He1, Chang Xu2, Zhao Cheng1
1School of Pharmacy, Xi'an Medical University, Xi'an, Shaanxi, China.
Abstract:
KRAS is the most common oncogene to be mutated in lung cancer, and therapeutics directly targeting KRAS have proven to be challenging. The mutations of KRAS are associated with poor prognosis, and resistance to both adjuvant therapy and targeted EGFR TKI. EGFR TKIs provide significant clinical benefit for patients whose tumors bear EGFR mutations. However, tumors with KRAS mutations rarely respond to the EGFR TKI therapy. Thus, 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 one of the best options at present to treat KRAS mutant lung cancer.
Insights
Targeting KRAS mutations in lung cancer is difficult. Combination therapies, including EGFR TKI with other agents, show promise for treating KRAS-mutant lung cancer, offering better outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- KRAS mutations are prevalent in lung cancer, correlating with poor prognosis and resistance to therapies like EGFR TKI.
- Tumors with KRAS mutations typically exhibit limited response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs).
Purpose of the Study:
- To review and evaluate combination therapeutic strategies for KRAS-mutant lung cancer.
- To highlight the necessity of combination therapy due to the challenges in directly targeting KRAS.
Main Methods:
- Literature review of combination therapies involving EGFR TKIs with various agents.
- Analysis of combination treatments including inhibitors of MAPKs, PI3K/mTOR, HDAC, Wee1, PARP, CDK, Hsp90, miRNAs, and immunotherapy.
Main Results:
- Combination therapies, while varying in efficacy, represent a key strategy for KRAS-mutant lung cancer.
- EGFR TKIs show limited efficacy alone in KRAS-mutant lung cancer, underscoring the need for combined approaches.
Conclusions:
- Combination therapy is essential for effectively treating lung cancers harboring KRAS mutations.
- Exploring combinations of EGFR TKIs with other targeted agents and immunotherapies offers a promising therapeutic avenue.
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