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Targeting KRAS

KRAS is one of the top genes mutated in cancer, making it a desirable therapeutic target for many tumor types. Research efforts over the last 40 years have provided new biologic insight into the function of this oncogene in cancer with recent work focusing on the development of effective KRAS-mutant specific inhibitors. These endeavors contributed to the discovery of inhibitors of KRASG12C, but nearly 85% of KRAS-mutated cancer continue to need effective therapies. This collection of articles highlights recent developments to the understanding of KRAS mutation landscapes across cancer, reveals additional vulnerabilities of KRAS-driven cancers, provides further insight into KRASG12C inhibitors including mechanisms of resistance, and reports on a highly anticipated inhibitor which effectively targets the prevalent KRASG12D mutation. Bailee Sliker, PhD, Assistant Editor, Cancer Discovery (Bailee.Sliker@aacr.org)


Review

Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants

Marco H. Hofmann; Daniel Gerlach; Sandra Misale; Mark Petronczki; Norbert Kraut

Doi: 10.1158/2159-8290.CD-21-1331

Review

Classification of KRAS-Activating Mutations and the Implications for Therapeutic Intervention

Christian Johnson; Deborah L. Burkhart; Kevin M. Haigis

Doi: 10.1158/2159-8290.CD-22-0035

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Samantha B. Kemp; Noah Cheng; Nune Markosyan; Rina Sor; Il-Kyu Kim; Jill Hallin; Jason Shoush; Liz Quinones; Natalie V. Brown; Jared B. Bassett; Nikhil Joshi; Salina Yuan; Molly Smith; William P. Vostrejs; Kia Z. Perez-Vale; Benjamin Kahn; Feiyan Mo; Timothy R. Donahue; Caius G. Radu; Cynthia Clendenin; James G. Christensen; Robert H. Vonderheide; Ben Z. Stanger
Robert B. Scharpf; Archana Balan; Biagio Ricciuti; Jacob Fiksel; Christopher Cherry; Chenguang Wang; Michele L. Lenoue-Newton; Hira A. Rizvi; James R. White; Alexander S. Baras; Jordan Anaya; Blair V. Landon; Marta Majcherska-Agrawal; Paola Ghanem; Jocelyn Lee; Leon Raskin; Andrew S. Park; Huakang Tu; Hil Hsu; Kathryn C. Arbour; Mark M. Awad; Gregory J. Riely; Christine M. Lovly; Valsamo Anagnostou
Seo-Hyun Choi; Jin K. Kim; Chin-Tung Chen; Chao Wu; Michael R. Marco; Francisco M. Barriga; Kevin O'Rourke; Raphael Pelossof; Xuan Qu; Qing Chang; Elisa de Stanchina; Jinru Shia; J. Joshua Smith; Francisco Sanchez-Vega; Julio Garcia-Aguilar
Andreas Weiss; Edwige Lorthiois; Louise Barys; Kim S. Beyer; Claudio Bomio-Confaglia; Heather Burks; Xueying Chen; Xiaoming Cui; Ruben de Kanter; Lekshmi Dharmarajan; Carmine Fedele; Marc Gerspacher; Daniel Alexander Guthy; Victoria Head; Ashley Jaeger; Eloísa Jiménez Núñez; Jeffrey D. Kearns; Catherine Leblanc; Sauveur-Michel Maira; Jason Murphy; Helen Oakman; Nils Ostermann; Johannes Ottl; Pascal Rigollier; Danielle Roman; Christian Schnell; Richard Sedrani; Toshio Shimizu; Rowan Stringer; Andrea Vaupel; Hans Voshol; Peter Wessels; Toni Widmer; Rainer Wilcken; Kun Xu; Frederic Zecri; Anna F. Farago; Simona Cotesta; Saskia M. Brachmann
Husain Yar Khan; Misako Nagasaka; Yiwei Li; Amro Aboukameel; Md. Hafiz Uddin; Rachel Sexton; Sahar Bannoura; Yousef Mzannar; Mohammed Najeeb Al-Hallak; Steve Kim; Rafic Beydoun; Yosef Landesman; Hirva Mamdani; Dipesh Uprety; Philip A. Philip; Ramzi M. Mohammad; Anthony F. Shields; Asfar S. Azmi
Biagio Ricciuti; Jieun Son; Jeffrey J. Okoro; Alessia Mira; Enrico Patrucco; Yoonji Eum; Xinan Wang; Raymond Paranal; Haiyun Wang; Mika Lin; Heidi M. Haikala; Jiaqi Li; Yue Xu; Joao Victor Alessi; Chhayheng Chhoeu; Amanda J. Redig; Jens Köhler; Kshiti H. Dholakia; Yunhan Chen; Elodie Richard; Marie-Julie Nokin; David Santamaria; Prafulla C. Gokhale; Mark M. Awad; Pasi A. Jänne; Chiara Ambrogio
Julia Judd; Nagla Abdel Karim; Hina Khan; Abdul Rafeh Naqash; Yasmine Baca; Joanne Xiu; Ari M. VanderWalde; Hirva Mamdani; Luis E. Raez; Misako Nagasaka; Sachin Gopalkrishna Pai; Mark A. Socinski; Jorge J. Nieva; Chul Kim; Antoinette J. Wozniak; Chukwuemeka Ikpeazu; Gilberto de Lima Lopes, Jr; Alexander I. Spira; W. Michael Korn; Edward S. Kim; Stephen V. Liu; Hossein Borghaei
Noritaka Tanaka; Jessica J. Lin; Chendi Li; Meagan B. Ryan; Junbing Zhang; Lesli A. Kiedrowski; Alexa G. Michel; Mohammed U. Syed; Katerina A. Fella; Mustafa Sakhi; Islam Baiev; Dejan Juric; Justin F. Gainor; Samuel J. Klempner; Jochen K. Lennerz; Giulia Siravegna; Liron Bar-Peled; Aaron N. Hata; Rebecca S. Heist; Ryan B. Corcoran
Michael P. Kim; Xinqun Li; Jenying Deng; Yun Zhang; Bingbing Dai; Kendra L. Allton; Tara G. Hughes; Christian Siangco; Jithesh J. Augustine; Ya'an Kang; Joy M. McDaniel; Shunbin Xiong; Eugene J. Koay; Florencia McAllister; Christopher A. Bristow; Timothy P. Heffernan; Anirban Maitra; Bin Liu; Michelle C. Barton; Amanda R. Wasylishen; Jason B. Fleming; Guillermina Lozano
Aslamuzzaman Kazi; Liwei Chen; Shengyan Xiang; Rajanikanth Vangipurapu; Hua Yang; Francisca Beato; Bin Fang; Terence M. Williams; Kazim Husain; Patrick Underwood; Jason B. Fleming; Mokenge Malafa; Eric A. Welsh; John Koomen; José Trevino; Saïd M. Sebti
David M. Briere; Shuai Li; Andrew Calinisan; Niranjan Sudhakar; Ruth Aranda; Lauren Hargis; David H. Peng; Jiehui Deng; Lars D. Engstrom; Jill Hallin; Sole Gatto; Julio Fernandez-Banet; Adam Pavlicek; Kwok-Kin Wong; James G. Christensen; Peter Olson
Marco H. Hofmann; Michael Gmachl; Juergen Ramharter; Fabio Savarese; Daniel Gerlach; Joseph R. Marszalek; Michael P. Sanderson; Dirk Kessler; Francesca Trapani; Heribert Arnhof; Klaus Rumpel; Dana-Adriana Botesteanu; Peter Ettmayer; Thomas Gerstberger; Christiane Kofink; Tobias Wunberg; Andreas Zoephel; Szu-Chin Fu; Jessica L. Teh; Jark Böttcher; Nikolai Pototschnig; Franziska Schachinger; Katharina Schipany; Simone Lieb; Christopher P. Vellano; Jonathan C. O'Connell; Rachel L. Mendes; Jurgen Moll; Mark Petronczki; Timothy P. Heffernan; Mark Pearson; Darryl B. McConnell; Norbert Kraut
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