Targeting Cancer

Symposium Participants v Foreword xvii

Cancer Stem Cells

Normal and Neoplastic Stem Cells Melissa N. McCracken, Benson M. George, Kevin S. Kao, Kristopher D. Marjon, Tal Raveh, and Irving L. Weissman 1 Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy Diwakar R. Pattabiraman and Robert A. Weinberg 11 Trimming the Vascular Tree in Tumors: Metabolic and Immune Adaptations Elizabeth Allen, Rindert Missiaen, and Gabriele Bergers 21 Cell of Origin and Cancer Stem Cells in Tumor Suppressor Mouse Models of Glioblastoma Sheila R. Alcantara Llaguno, Xuanhua Xie, and Luis F. Parada 31

Genetics and Epigenetics

The Enigma of p53 Guillermina Lozano 37 Alterations in Three-Dimensional Organization of the Cancer Genome and Epigenome Joanna Achinger-Kawecka, Phillippa C. Taberlay, and Susan J. Clark 41 Composition and Function of Mammalian SWI/SNF Chromatin Remodeling Complexes in Human Disease John L. Pulice and Cigall Kadoch 53 The Essential Transcriptional Function of BRD4 in Acute Myeloid Leukemia Jae-Seok Roe and Christopher R. Vakoc 61

Metabolism

Reexamining How Cancer Cells Exploit the Body’s Metabolic Resources Craig B. Thompson and Wilhelm Palm 67 Autophagy, Metabolism, and Cancer Jessie Yanxiang Guo and Eileen White 73 A Time for MYC: Metabolism and Therapy Chi V. Dang 79 Beyond the Oncogene Revolution: Four New Ways to Combat Cancer Thorsten Berger, Mary E. Saunders, and Tak W. Mak 85 Lipid Synthesis Is a Metabolic Liability of Non–Small Cell Lung Cancer Robert U. Svensson and Reuben J. Shaw 93

Targets, Vaccines, and Therapeutics

Cancer Immunogenomics: Computational Neoantigen Identification and Vaccine Design Jasreet Hundal, Christopher A. Miller, Malachi Griffith, Obi L. Griffith, Jason Walker, Susanna Kiwala, Aaron Graubert, Joshua McMichael, Adam Coffman, and Elaine R. Mardis 105 Targeting HIF2 in Clear Cell Renal Cell Carcinoma Hyejin Cho and William G. Kaelin 113 BET Bromodomain Proteins as Cancer Therapeutic Targets Shaokun Shu and Kornelia Polyak 123 To Prime, or Not to Prime: That Is the Question Danielle S. Potter and Anthony Letai 131 Genetic Dissection of Cancer Development, Therapy Response, and Resistance in Mouse Models of Breast Cancer Stefano Annunziato, Marco Barazas, Sven Rottenberg, and Jos Jonkers 141

Microenvironment and Metastasis

Tumor–Stroma Interactions in Bone Metastasis: Molecular Mechanisms and Therapeutic Implications Hanqiu Zheng, Wenyang Li, and Yibin Kang 151 Cancer, Oxidative Stress, and Metastasis Jennifer G. Gill, Elena Piskounova, and Sean J. Morrison 163 RON Signaling Is a Key Mediator of Tumor Progression in Many Human Cancers Najme Faham and Alana L. Welm 177 Physical and Chemical Gradients in the Tumor Microenvironment Regulate Tumor Cell Invasion, Migration, and Metastasis Madeleine J. Oudin and Valerie M. Weaver 189

Models of Cancer

Pathways Involved in Formation of Mammary Organoid Architecture Have Keys to Understanding Drug Resistance and to Discovery of Druggable Targets Saori Furuta and Mina J. Bissell 207 Explaining the Paucity of Intratumoral T Cells: A Construction Out of Known Entities Douglas T. Fearon 219 Modeling Breast Cancer Intertumor and Intratumour Heterogeneity Using Xenografts Alejandra Bruna, Oscar M. Rueda, and Carlos Caldas 227 Challenges and Opportunities in Modeling Pancreatic Cancer Michael E. Feigin and David A. Tuveson 231

Cancer Genomics and Tumor Heterogeneity

Functional Genomic Characterization of Cancer Genomes Thomas P. Howard, Francisca Vazquez, Aviad Tsherniak, Andrew L. Hong, Mik Rinne, Andrew J. Aguirre, Jesse S. Boehm, and William C. Hahn 237 How Cancer Genomics Drives Cancer Biology: Does Synthetic Lethality Explain Mutually Exclusive Oncogenic Mutations? Harold Varmus, Arun M. Unni, and William W. Lockwood 247 A Pipeline for Drug Target Identification and Validation Eusebio Manchado, Chun-Hao Huang, Nilgun Tasdemir, Darjus F. Tschaharganeh, John E. Wilkinson, and Scott W. Lowe 257 Single-Cell Analysis of Circulating Tumor Cells as a Window into Tumor Heterogeneity David T. Miyamoto, David T. Ting, Mehmet Toner, Shyamala Maheswaran, and Daniel A. Haber 269 Discovery of Double-Stranded Genomic DNA in Circulating Exosomes Raghu Kalluri and Valerie S. LeBleu 275

Summary

Moving Closer to Victory Taru Muranen and Joan S. Brugge 281

Dorcas Cummings Lecture 289

Charles Sawyers 291

Conversations at the Symposium 297

Gabriele Bergers 299 Joan Brugge 301 Karen Cichowski 304 Susan Clark 306 Gerard Evan 309 Daniel Haber 311 William Kaelin 314 Raghu Kalluri 317 Scott Lowe 320 Guillermina (Gigi) Lozano 323 David Lyden 326 Elaine Mardis 328 Sean Morrison 331 Benjamin Neel 334 Luis Parada 336 Sir Michael Stratton 338 David Tuveson 341 Christopher Vakoc 344 Harold Varmus 347 Karen Vousden 351 Valerie Weaver 354 Robert Weinberg 357 Eileen White 360

Author Index 363

Subject Index 365