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From the Current Issue

  • 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
    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 | 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.

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