Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future
1
Department of Pharmacology, Center of Physiology and Pharmacology & Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria
2
Department of Physiology, Center of Physiology and Pharmacology & Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria
3
Ludwig Boltzmann Institute for Cancer Research (LBI-CR), 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(12), 4325; https://doi.org/10.3390/ijms21124325
Received: 13 May 2020
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Revised: 8 June 2020
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Accepted: 11 June 2020
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Published: 17 June 2020
(This article belongs to the Special Issue Kinase Signal Transduction 2020)
Lung cancer is the most frequent cancer with an aggressive clinical course and high mortality rates. Most cases are diagnosed at advanced stages when treatment options are limited and the efficacy of chemotherapy is poor. The disease has a complex and heterogeneous background with non-small-cell lung cancer (NSCLC) accounting for 85% of patients and lung adenocarcinoma being the most common histological subtype. Almost 30% of adenocarcinomas of the lung are driven by an activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. The ability to inhibit the oncogenic KRAS has been the holy grail of cancer research and the search for inhibitors is immensely ongoing as KRAS-mutated tumors are among the most aggressive and refractory to treatment. Therapeutic strategies tailored for KRAS+ NSCLC rely on the blockage of KRAS functional output, cellular dependencies, metabolic features, KRAS membrane associations, direct targeting of KRAS and immunotherapy. In this review, we provide an update on the most recent advances in anti-KRAS therapy for lung tumors with mechanistic insights into biological diversity and potential clinical implications.
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Keywords:
lung adenocarcinoma; NSCLC; KRAS; targeted therapy; immunotherapy; metabolic rewiring; p53; STK11; EGFR; degraders
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MDPI and ACS Style
Uras, I.Z.; Moll, H.P.; Casanova, E. Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future. Int. J. Mol. Sci. 2020, 21, 4325. https://doi.org/10.3390/ijms21124325
AMA Style
Uras IZ, Moll HP, Casanova E. Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future. International Journal of Molecular Sciences. 2020; 21(12):4325. https://doi.org/10.3390/ijms21124325
Chicago/Turabian StyleUras, Iris Z., Herwig P. Moll, and Emilio Casanova. 2020. "Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future" International Journal of Molecular Sciences 21, no. 12: 4325. https://doi.org/10.3390/ijms21124325
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