Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Undruggable proteins are a class of proteins that are often characterized by large, complex
structures or functions that are difficult to interfere with using conventional drug design …
structures or functions that are difficult to interfere with using conventional drug design …
KRAS mutation in pancreatic cancer
J Luo - Seminars in oncology, 2021 - Elsevier
Pancreatic cancer is a recalcitrant cancer with one of the lowest 5-year survival rates. A
hallmark of pancreatic cancer is the prevalence of oncogenic mutation in the KRAS gene …
hallmark of pancreatic cancer is the prevalence of oncogenic mutation in the KRAS gene …
BI-3406, a potent and selective SOS1–KRAS interaction inhibitor, is effective in KRAS-driven cancers through combined MEK inhibition
MH Hofmann, M Gmachl, J Ramharter, F Savarese… - Cancer Discovery, 2021 - AACR
KRAS is the most frequently mutated driver of pancreatic, colorectal, and non–small cell lung
cancers. Direct KRAS blockade has proved challenging, and inhibition of a key downstream …
cancers. Direct KRAS blockade has proved challenging, and inhibition of a key downstream …
Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS-and autophagy-
dependent tumorigenic growth, but the role of KRAS in supporting autophagy has not been …
dependent tumorigenic growth, but the role of KRAS in supporting autophagy has not been …
The dTAG system for immediate and target-specific protein degradation
Dissection of complex biological systems requires target-specific control of the function or
abundance of proteins. Genetic perturbations are limited by off-target effects …
abundance of proteins. Genetic perturbations are limited by off-target effects …
Cancer gene mutation frequencies for the US population
G Mendiratta, E Ke, M Aziz, D Liarakos, M Tong… - Nature …, 2021 - nature.com
Mutations play a fundamental role in the development of cancer, and many create targetable
vulnerabilities. There are both public health and basic science benefits from the …
vulnerabilities. There are both public health and basic science benefits from the …
RAS proteins and their regulators in human disease
DK Simanshu, DV Nissley, F McCormick - Cell, 2017 - cell.com
RAS proteins are binary switches, cycling between ON and OFF states during signal
transduction. These switches are normally tightly controlled, but in RAS-related diseases …
transduction. These switches are normally tightly controlled, but in RAS-related diseases …
KRAS: the critical driver and therapeutic target for pancreatic cancer
RAS genes (HRAS, KRAS, and NRAS) comprise the most frequently mutated oncogene
family in human cancer. With the highest RAS mutation frequencies seen with the top three …
family in human cancer. With the highest RAS mutation frequencies seen with the top three …
SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling
KRAS is the most frequently mutated human oncogene, and KRAS inhibition has been a
longtime goal. Recently, inhibitors were developed that bind KRASG12C-GDP and react …
longtime goal. Recently, inhibitors were developed that bind KRASG12C-GDP and react …
Drugging the'undruggable'cancer targets
The term'undruggable'was coined to describe proteins that could not be targeted
pharmacologically. However, progress is being made to'drug'many of these targets, and …
pharmacologically. However, progress is being made to'drug'many of these targets, and …