TY - JOUR
T1 - Targeting the undruggable oncogenic KRAS
T2 - The dawn of hope
AU - Asimgil, Hande
AU - Ertetik, Utku
AU - Çevik, Nedim Can
AU - Ekizce, Menar
AU - Doǧruöz, Alper
AU - Gökalp, Muazzez
AU - Arik-Sever, Elif
AU - Istvanffy, Rouzanna
AU - Friess, Helmut
AU - Ceyhan, Güralp Onur
AU - Demir, Ihsan Ekin
N1 - Publisher Copyright:
© 2022, Asimgil et al.
PY - 2022/1/11
Y1 - 2022/1/11
N2 - KRAS mutations are the drivers of various cancers, including non-small cell lung cancer, colon cancer, and pancreatic cancer. Over the last 30 years, immense efforts have been made to inhibit KRAS mutants and oncogenic KRAS signaling using inhibitors. Recently, specific targeting of KRAS mutants with small molecules revived the hopes for successful therapies for lung, pancreatic, and colorectal cancer patients. Moreover, advances in gene editing, protein engineering, and drug delivery formulations have revolutionized cancer therapy regimens. New therapies aim to improve immune surveillance and enhance antitumor immunity by precisely targeting cancer cells harboring oncogenic KRAS. Here, we review recent KRAS-targeting strategies, their therapeutic potential, and remaining challenges to overcome. We also highlight the potential synergistic effects of various combinatorial therapies in preclinical and clinical trials.
AB - KRAS mutations are the drivers of various cancers, including non-small cell lung cancer, colon cancer, and pancreatic cancer. Over the last 30 years, immense efforts have been made to inhibit KRAS mutants and oncogenic KRAS signaling using inhibitors. Recently, specific targeting of KRAS mutants with small molecules revived the hopes for successful therapies for lung, pancreatic, and colorectal cancer patients. Moreover, advances in gene editing, protein engineering, and drug delivery formulations have revolutionized cancer therapy regimens. New therapies aim to improve immune surveillance and enhance antitumor immunity by precisely targeting cancer cells harboring oncogenic KRAS. Here, we review recent KRAS-targeting strategies, their therapeutic potential, and remaining challenges to overcome. We also highlight the potential synergistic effects of various combinatorial therapies in preclinical and clinical trials.
UR - http://www.scopus.com/inward/record.url?scp=85123121044&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.153688
DO - 10.1172/jci.insight.153688
M3 - Review article
C2 - 35014625
AN - SCOPUS:85123121044
SN - 2379-3708
VL - 7
JO - JCI Insight
JF - JCI Insight
IS - 1
M1 - e153688
ER -
