Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future.
Iris Z UrasHerwig P MollEmilio CasanovaPublished in: International journal of molecular sciences (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.
Keyphrases
- wild type
- small cell lung cancer
- end stage renal disease
- papillary thyroid
- chronic kidney disease
- ejection fraction
- newly diagnosed
- oxidative stress
- sars cov
- prognostic factors
- squamous cell carcinoma
- signaling pathway
- risk factors
- coronary artery disease
- peritoneal dialysis
- transcription factor
- young adults
- advanced non small cell lung cancer
- tyrosine kinase
- brain metastases