Table of Contents

Research Articles

• Research Articles | AuthorChoice

  First-in-Human Trial of the Oral Ataxia Telangiectasia and RAD3-Related (ATR) Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors

  Timothy A. Yap, David S.P. Tan, Angelika Terbuch, Reece Caldwell, Christina Guo, Boon Cher Goh, Valerie Heong, Noor R. Md. Haris, Saira Bashir, Yvette Drew, David S. Hong, Funda Meric-Bernstam, Gary Wilkinson, Joseph Hreiki, Antje M. Wengner, Friedhelm Bladt, Andreas Schlicker, Matthias Ludwig, Yinghui Zhou, Li Liu, Sonal Bordia, Ruth Plummer, Eleni Lagkadinou and Johann S. de Bono

  Cancer Discov January 1 2021 11 (1) 80-91; DOI:10.1158/2159-8290.CD-20-0868

  
  

  In a phase I trial, the ATR inhibitor BAY 1895344 showed preliminary evidence of efficacy against advanced solid tumors, particularly those with low ATM protein levels and/or ATM mutations.

• Research Articles | AuthorChoice

  Triplet Therapy with Palbociclib, Taselisib, and Fulvestrant in PIK3CA-Mutant Breast Cancer and Doublet Palbociclib and Taselisib in Pathway-Mutant Solid Cancers

  Javier Pascual, Joline S.J. Lim, Iain R. Macpherson, Anne C. Armstrong, Alistair Ring, Alicia F.C. Okines, Rosalind J. Cutts, Maria Teresa Herrera-Abreu, Isaac Garcia-Murillas, Alex Pearson, Sarah Hrebien, Heidrun Gevensleben, Paula Z. Proszek, Michael Hubank, Margaret Hills, Jenny King, Mona Parmar, Toby Prout, Laura Finneran, Jason Malia, Karen E. Swales, Ruth Ruddle, Florence I. Raynaud, Alison Turner, Emma Hall, Timothy A. Yap, Juanita S. Lopez and Nicholas C. Turner

  Cancer Discov January 1 2021 11 (1) 92-107; DOI:10.1158/2159-8290.CD-20-0553

  
  

  Supporting preclinical data that showed synergy between CDK4/6 inhibitors and PI3K inhibitors in PI3KCA-mutant, estrogen receptor–positive, HER2-negative breast cancer, a phase Ib trial found corresponding results in patients with advanced disease.

• Research Articles

  Resistance to Avapritinib in PDGFRA-Driven GIST Is Caused by Secondary Mutations in the PDGFRA Kinase Domain

  Susanne Grunewald, Lillian R. Klug, Thomas Mühlenberg, Jonas Lategahn, Johanna Falkenhorst, Ajia Town, Christiane Ehrt, Eva Wardelmann, Wolfgang Hartmann, Hans-Ulrich Schildhaus, Juergen Treckmann, Jonathan A. Fletcher, Sascha Jung, Paul Czodrowski, Stephen Miller, Oleg Schmidt-Kittler, Daniel Rauh, Michael C. Heinrich and Sebastian Bauer

  Cancer Discov January 1 2021 11 (1) 108-125; DOI:10.1158/2159-8290.CD-20-0487

  
  

  PDGFRA-mutant gastrointestinal stromal tumors that develop resistance to PDGFRA inhibition harbored secondary mutations in the PDGFRA kinase domain, and these tumors were still dependent on oncogenic PDGFRA signaling.

• Research Articles

  TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors

  Emiliano Cocco, Ji Eun Lee, Srinivasaraghavan Kannan, Alison M. Schram, Helen H. Won, Sophie Shifman, Amanda Kulick, Laura Baldino, Eneda Toska, Amaia Arruabarrena-Aristorena, Srushti Kittane, Fan Wu, Yanyan Cai, Sabrina Arena, Benedetta Mussolin, Ram Kannan, Neil Vasan, Alexander N. Gorelick, Michael F. Berger, Ofra Novoplansky, Sankar Jagadeeshan, Yi Liao, Uwe Rix, Sandra Misale, Barry S. Taylor, Alberto Bardelli, Jaclyn F. Hechtman, David M. Hyman, Moshe Elkabets, Elisa de Stanchina, Chandra S. Verma, Andrea Ventura, Alexander Drilon and Maurizio Scaltriti

  Cancer Discov January 1 2021 11 (1) 126-141; DOI:10.1158/2159-8290.CD-20-0571

  
  

  Mutations that cause resistance to type I tyrosine kinase inhibitors (TKI) in TRK fusion–positive cancer caused sensitivity to type II TKIs because these mutations stabilized the inactive “DFG-out” conformation of TRK, which is bound by type II TKIs.

• Research Articles | AuthorChoice

  BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition

  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 and Norbert Kraut

  Cancer Discov January 1 2021 11 (1) 142-157; DOI:10.1158/2159-8290.CD-20-0142

  
  

  A novel small-molecule drug, BI-3406, was used to block interactions between KRAS and the guanine exchange factor SOS1, hindering GTP binding by KRAS and thus reducing its activity to prevent tumor cell growth in vitro and in vivo.

• Research Articles | AuthorChoice

  Antibody to CD137 Activated by Extracellular Adenosine Triphosphate Is Tumor Selective and Broadly Effective In Vivo without Systemic Immune Activation

  Mika Kamata-Sakurai, Yoshinori Narita, Yuji Hori, Takayuki Nemoto, Ryo Uchikawa, Masaki Honda, Naoka Hironiwa, Kenji Taniguchi, Meiri Shida-Kawazoe, Shoichi Metsugi, Taro Miyazaki, Naoko A. Wada, Yuki Ohte, Shun Shimizu, Hirofumi Mikami, Tatsuhiko Tachibana, Natsuki Ono, Kenji Adachi, Tetsushi Sakiyama, Tomochika Matsushita, Shojiro Kadono, Shun-ichiro Komatsu, Akihisa Sakamoto, Sayuri Horikawa, Ayano Hirako, Koki Hamada, Sotaro Naoi, Nasa Savory, Yasuko Satoh, Motohiko Sato, Yuki Noguchi, Junko Shinozuka, Haruka Kuroi, Ami Ito, Tetsuya Wakabayashi, Masaki Kamimura, Fumihisa Isomura, Yasushi Tomii, Noriaki Sawada, Atsuhiko Kato, Otoya Ueda, Yoshito Nakanishi, Mika Endo, Kou-ichi Jishage, Yoshiki Kawabe, Takehisa Kitazawa and Tomoyuki Igawa

  Cancer Discov January 1 2021 11 (1) 158-175; DOI:10.1158/2159-8290.CD-20-0328

  
  

  An extracellular ATP–activated agonistic antibody to CD137, which promotes T-cell survival and proliferation, showed antitumor efficacy in multiple in vivo models, causing T-cell activation within tumors without off-target toxicity.

• Research Articles

  Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death

  Stephen Sakuma, Marcela Raices, Joana Borlido, Valeria Guglielmi, Ethan Y.S. Zhu and Maximiliano A. D'Angelo

  Cancer Discov January 1 2021 11 (1) 176-193; DOI:10.1158/2159-8290.CD-20-0581

  
  

  In vitro and in vivo, depletion of components of the nuclear pore complex (NPC) preferentially killed cancer cells, sparing normal cells, by causing nuclear transport aberrations, gene expression changes, and DNA damage.

• Research Articles

  An Epigenetic Mechanism Underlying Chromosome 17p Deletion–Driven Tumorigenesis

  Mei Chen, Xuelan Chen, Shujun Li, Xiangyu Pan, Yanqiu Gong, Jianan Zheng, Jing Xu, Chengjian Zhao, Qi Zhang, Shan Zhang, Lu Qi, Zhongwang Wang, Kaidou Shi, Bi-Sen Ding, Zhihong Xue, Lu Chen, Shengyong Yang, Yuan Wang, Ting Niu, Lunzhi Dai, Scott W. Lowe, Chong Chen and Yu Liu

  Cancer Discov January 1 2021 11 (1) 194-207; DOI:10.1158/2159-8290.CD-20-0336

  
  

  Loss of the gene encoding the putative epigenetic reader PHF23, which formed a complex with the SIN3–HDAC histone deacetylase complex and reduced its activity, was a major driver of chromosome 17p loss–driven tumorigenesis.