Jänne, P.A., Shaw, A.T., Pereira, J.R., Jeannin, G., Vansteenkiste, J., Barrios, C., Franke, F.A., Grinsted, L., Zazulina, V. and Smith, P. (2013) Selumetinib plus Docetaxel for KRAS-Mutant Advanced Non-Small-Cell Lung Cancer: A Randomised, Multicentre, Placebo-Controlled, Phase 2 Study. The Lancet Oncology, 14, 38-47.
https://doi.org/10.1016/S1470-2045(12)70489-8

has been cited by the following article:

• TITLE: Exploration of Kras Mutations and Their Potential for Being a Target Molecule in Cancer Chemotherapy

  AUTHORS: Anusha Chinthareddy, Terry Oroszi

  KEYWORDS: KRAS Mutations, Non-Small Cell Lung Carcinoma (NSCLC), Colorectal Can-cer, MAPK Pathway, Chemotherapy

  JOURNAL NAME: Journal of Cancer Therapy, Vol.14 No.6, June 16, 2023

  ABSTRACT: The Rat sarcoma virus (RAS) family of proteins, which includes the Kristen Rat sarcoma virus (KRAS), is linked to nearly one-fourth of all human cancers. KRAS mutations, in particular, are associated with Non-Small Cell Lung Carcinoma (NSCLC), colorectal cancer, adenocarcinomas, ovarian carcinoma, and endometrial tumors. KRAS activates 80 different signaling pathways, including Mitogen-activated protein kinases (MAPK) and Phosphoinositide 3-kinase (PI3K), and up-regulates transcription factors such as ETS like Protein (ELK), Jun Proto-Oncogene (JUN), and Myelocytomatosis (MYC), which are involved in cell differentiation, proliferation, transformation, and survival. KRAS mutations are also known to cause autocrine function, which further exacerbates the situation. In NSCLC, KRAS mutations have a strong positive correlation with the disease, particularly in patients with a smoking history. In pancreatic cancer, KRAS mutations are a dominant pathological basis, with most mutations being G12D, G12V, G13D, G13C, G13S, and G13R. These mutations serve as initial markers in tumorigenesis and are associated with poor prognosis and high mortality rates. In colorectal cancer, KRAS mutations contribute to 4/5 of cases, with cellular mechanisms involving the MAPK pathway, which resists anti-epidermal growth factor antibodies. In Low-grade Serous Ovarian Cancer (LGSOC), KRAS mutations are associated with altered signaling in the MAPK pathway and drug resistance. However, treatments such as Selumetinib, a down regulator of RAS/Rapidly Accelerated Fibrosarcoma (RAF)/Mitogen-activated protein kinase (MEK) pathways, and a combination of trametinib and buparlisib have shown promise in managing LGSOC when diagnosed early through KRAS mutation markers. Although KRAS mutations are commonly associated with many types of cancer, their use in clinical practice is limited due to the lack of accurate methods to identify them. It is needed to further isolate the KRAS mutation products and correlate the cancer-causing genes to make it a promising approach for cancer chemotherapy.