KEAP1-Dependent Synthetic Lethality Induced by AKT and TXNRD1 Inhibitors in Lung Cancer

KEAP1-dependent synthetic lethality induced by AKT and TXNRD1 inhibitors in lung cancer.

Intrinsic resistance to agents targeting phosphoinositide 3-kinase (PI3K)/AKT pathway is one of the major challenges in cancer treatment with such agents. The objective of this study is to identify the genes or pathways that can be targeted to overcome the resistance of non-small cell lung carcinoma (NSCLC) to the AKT inhibitor MK2206, which is currently being evaluated in phase I and II clinic...

Protease Addiction and Synthetic Lethality in Cancer

The "oncogene addiction" concept refers to the dependence of cancer cells on the function of the oncogenes responsible for their transformed phenotype, while the term "non-oncogene addiction" has been introduced to define the exacerbated necessity of the normal function of non-mutated genes. In this Perspective, we focus on the importance of proteolytic enzymes to maintain the viability of canc...

caspase-dependent pathway in apoptosis induced by safranal in alveolar human lung cancer cell line

Suppression of AKT phosphorylation restores rapamycin-based synthetic lethality in SMAD4-defective pancreatic cancer cells.

mTOR has been implicated in survival signals for many human cancers. Rapamycin and TGF-β synergistically induce G1 cell-cycle arrest in several cell lines with intact TGF-β signaling pathway, which protects cells from the apoptotic effects of rapamycin during S-phase of the cell cycle. Thus, rapamycin is cytostatic in the presence of serum/TGF-β and cytotoxic in the absence of serum. However, i...

Keap1 mutations in lung cancer patients

Kelch-like ECH-associated protein 1 (Keap1) inhibits nuclear factor erythroid 2-related 2 (NEF2L2; also named NRF2)-induced cytoprotection and has been hypothesized to represent a candidate tumor suppressor. We have previously reported the somatic mutations of the NRF2 gene (NFE2L2), however, the correlation between the Keap1 mutation and the clinicopathological features of lung cancer has not ...