[HTML][HTML] Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges

D Tang, G Kroemer, R Kang - Molecular cancer, 2021 - Springer
Across a broad range of human cancers, gain-of-function mutations in RAS genes (HRAS,
NRAS, and KRAS) lead to constitutive activity of oncoproteins responsible for tumorigenesis …

[HTML][HTML] Epitranscriptomics and epiproteomics in cancer drug resistance: therapeutic implications

H Song, D Liu, S Dong, L Zeng, Z Wu, P Zhao… - Signal transduction and …, 2020 - nature.com
Drug resistance is a major hurdle in cancer treatment and a key cause of poor prognosis.
Epitranscriptomics and epiproteomics are crucial in cell proliferation, migration, invasion …

Clinical Acquired Resistance to KRASG12C Inhibition through a Novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS–MAPK …

N Tanaka, JJ Lin, C Li, MB Ryan, J Zhang… - Cancer discovery, 2021 - AACR
Mutant-selective KRASG12C inhibitors, such as MRTX849 (adagrasib) and AMG 510
(sotorasib), have demonstrated efficacy in KRAS G12C-mutant cancers, including non–small …

Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS

CJ Schulze, KJ Seamon, Y Zhao, YC Yang, J Cregg… - Science, 2023 - science.org
The discovery of small-molecule inhibitors requires suitable binding pockets on protein
surfaces. Proteins that lack this feature are considered undruggable and require innovative …

[HTML][HTML] The KRAS-G12C inhibitor: activity and resistance

J Liu, R Kang, D Tang - Cancer gene therapy, 2022 - nature.com
Although it has long been deemed “undruggable”, with the development of drugs specifically
binding the KRAS-G12C mutant protein, clinical trials that directly inhibit oncogenic RAS …

[HTML][HTML] Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer

L Aubert, N Nandagopal, Z Steinhart, G Lavoie… - Nature …, 2020 - nature.com
Despite its importance in human cancers, including colorectal cancers (CRC), oncogenic
KRAS has been extremely challenging to target therapeutically. To identify potential …

NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron–sulfur cluster proteins

N Santana-Codina, MQ Del Rey, KS Kapner, H Zhang… - Cancer discovery, 2022 - AACR
Pancreatic ductal adenocarcinomas (PDAC) depend on autophagy for survival; however,
the metabolic substrates that autophagy provides to drive PDAC progression are unclear …

Autophagy supports mitochondrial metabolism through the regulation of iron homeostasis in pancreatic cancer

S Mukhopadhyay, J Encarnación-Rosado, EY Lin… - Science …, 2023 - science.org
Pancreatic ductal adenocarcinoma (PDAC) cells maintain a high level of autophagy,
allowing them to thrive in an austere microenvironment. However, the processes through …

Coordinated transcriptional and catabolic programs support iron-dependent adaptation to RAS–MAPK pathway inhibition in pancreatic cancer

M Ravichandran, J Hu, C Cai, NP Ward, A Venida… - Cancer discovery, 2022 - AACR
The mechanisms underlying metabolic adaptation of pancreatic ductal adenocarcinoma
(PDA) cells to pharmacologic inhibition of RAS–MAPK signaling are largely unknown. Using …

[HTML][HTML] Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer

C Bartolacci, C Andreani, G Vale, S Berto… - Nature …, 2022 - nature.com
Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid
(FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently …