Targeted Therapy in Translational Cancer Research

Targeted Therapy in Translational Cancer Research for the Translational Oncology series provides a comprehensive overview of recent developments in our understanding of tumor biology, elucidates the roles of targets and pathways involved in carcinogenesis, and describes current state-of-the-art anticancer therapy, as well as the most promising areas of translational research and targeted therapy.

• Introduces cutting-edge ‘bench to bedside and back’ breakthroughs which have transformed the diagnosis, prognosis, and treatment of cancer
• Covers basic principles of targeted therapy, including immunotherapy and the roles of cancer stem cells, the microenvironment, angiogenesis, epigenetics, microRNAs, and functional imaging in precision medicine
• Summarises major advances in therapeutic management of hematologic malignancies and solid tumors using conventional therapy, targeted therapy, immunotherapy, or novel treatment modalities

List of Contributors, vii

Series Foreword, xiii

Foreword, xv

Preface, xvii

Part I Principles of Targeted Therapies

1 Toward Personalized Therapy for Cancer, 3
Ashley M. Holder and FundaMeric-Bernstam

2 Combining Targeted Therapies, 14
Jordi Rodon, Analia Azaro, Davis Torrejon, and Razelle Kurzrock

3 Principles of Targeted Immunotherapy, 27
Susanne H. C. Baumeister and Glenn Dranoff

4 Cancer Stem Cell Principles, 39
Allison C. Sharrow, Gabriel Ghiaur, and Richard J. Jones

5 The Tumor Microenvironment as a Target for Therapeutic Intervention, 47
Hua Fang and Yves A. DeClerck

6 The Role of Angiogenesis in Cancer, 64
Morgan Taylor, Robert L. Coleman, and Anil K. Sood

7 Epigenetics and Epigenetic Therapy of Cancer, 72
Omotayo Fasan, Patrick Boland, PatriciaKropf, and Jean-Pierre J. Issa

8 The Role of microRNAs in Cancer, 80
Gianpiero Di Leva and Carlo M. Croce

9 AcuteMyeloidLeukemia, 89
Ofir Wolach and Richard M. Stone

10 Targeted and Functional Imaging, 101
Jian Q. (Michael) Yu, Drew A. Torigian, and Abass Alavi

Part II Targeted Therapy in Hematological Malignancies

11 Targeted Therapies in Chronic Myeloid Leukemia, 113
Elias Jabbour and Jorge Cortes

12 Targeted Therapy for Acute Lymphoblastic Leukemia, 121
Nitin Jain, Susan O’Brien, and Farhad Ravandi-Kashani

13 Chronic Lymphocytic Leukemia, 130
Preetesh Jain and Susan O’Brien

14 Multiple Myeloma, 145
Giada Bianchi and Kenneth C. Anderson

15 The Impact of Genomics on Targeted Therapy in Multiple Myeloma and Lymphomas, 157
Jens G. Lohr and Birgit Knoechel

16 Targeted Therapy in Myelodysplastic Syndromes, 162
Guillermo Montalb´an-Bravo and Guillermo Garc´ýa-Manero

17 Lymphoma and Targeted Therapies, 169
Sonali M. Smith and Julie M. Vose

Part III Targeted Therapy in Solid Tumors

18 Targeted Therapy in Solid Tumors: Brain, 179
Shiao-PeiWeathers, Barbara J. O’Brien, John F. de Groot, andW. K. Alfred Yung

19 Targeted Therapy for Breast Cancer, 190
Harold J. Burstein

20 Targeted Therapy in Solid Tumors: Colorectal Cancer, 193
Maen Abdelrahim, Scott Kopetz, and David Menter

21 Endometrial Cancer, 205
Jessica L. Bowser, Russell R. Broaddus, Robert L. Coleman, and Shannon N. Westin

22 Targeted Therapy in Solid Tumors: Head and Neck, 216
Marcus M. Monroe and Jeffrey N. Myers

23 Targeted Therapy in Solid Tumors: Lung Cancer, 224
Saiama N.Waqar, Daniel Morgensztern, and Roy S. Herbst

24 Targeted Therapy in Melanoma, 231
Keith T. Flaherty

25 Ovarian Cancer, 240
Shannon N.Westin, Larissa A. Meyer, and Robert L. Coleman

26 Molecular Therapeutics: Pancreatic Cancer, 255
David Fogelman, Milind Javle, and James Abbruzzese

27 Targeted Therapies for Pediatric Solid Tumors, 263
Jasmine Quynh Dao and Patrick A. Zweidler-McKay

28 Prostate Cancer, 273
William G. Nelson, Michael C. Haffner, and Srinivasan Yegnasubramanian

29 Renal Cell Carcinoma and Targeted Therapy, 287
Benjamin A. Gartrell, Alexander C. Small, William K. Oh, and Matthew D. Galsky

30 Targeted Therapy in Solid Tumors: Sarcomas, 296
Anthony P. Conley, Vinod Ravi, and Shreyaskumar Patel

Part IV Targeted Therapy for Specific Molecular Aberrations

31 RAS-RAF-MEK Pathway: Aberrations and Therapeutic Possibilities, 305
Javier Munoz and Filip Janku

32 The Phosphatidylinositol 3-Kinase Pathway in Human Malignancies, 315
Samuel J. Klempner,Thanh-Trang Vo, Andrea P. Myers, and Lewis C. Cantley

33 Current Status and Future Direction of PARP Inhibition in Cancer Therapy, 325
Saeed Rafii, Stan Kaye and Susana Banerjee

34 Targeting the c-Met Kinase, 341
Chad Tang, M. Angelica Cortez, David Hong, and James W. Welsh

35 KIT Kinase, 347
Scott E. Woodman

36 TP53, 353
Kensuke Kojima and Michael Andreeff

Part V Future Perspectives

37 Future Perspectives, 363
Rabih Said and Apostolia-Maria Tsimberidou

Index, 371

Apostolia-Maria Tsimberidou, MD PhD
Department of Investigational Cancer Therapeutics
The University of Texas MD Anderson Cancer Center
Houston, TX, USA

Razelle Kurzrock
Center for Personalized Cancer Therapy, UC San Diego - Moores Cancer Center
La Jolla, CA, USA

Kenneth C. Anderson MD
LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School
Boston, MA, USA

In the last decade, emergent technologies have enhanced our understanding of genomic, transcriptional, proteomic, epigenetic, and immune mechanisms in carcinogenesis. This improved understanding has enabled the development of targeted cancer therapies and personalized management, and transformed conventional treatment paradigms. It has provided the framework for the discovery of new targets, for validation of novel agents, for combination therapies predicated upon scientific rationale, and for clinical trials that have already markedly improved the prognosis and outcome of patients with cancer.

Over 37 chapters this volume of Translational Oncology series, Targeted Therapy in Translational Cancer Research:

• Introduces the cutting-edge ‘bench to bedside and back’ breakthroughs which have transformed the diagnosis, prognosis, and treatment of cancer
• Provides a comprehensive overview of recent developments in our understanding of tumor biology and describes current state-of-the-art anticancer therapy, as well as the most promising areas of translational research and targeted therapy
• Covers basic principles of targeted therapy, including immunotherapy and the roles of cancer stem cells, the microenvironment, angiogenesis, epigenetics, microRNAs, and functional imaging in precision medicine
• Summarises major advances in therapeutic management of hematologic malignancies and solid tumors using conventional therapy, targeted therapy, immunotherapy, or novel treatment modalities

We are on the threshold of translating discoveries in cancer biology into unprecedented durable responses and improved clinical outcomes in the majority of patients with cancer. In this unique time in history, the discovery of novel therapeutic approaches targeting the molecular basis of cancer will allow for implementation of precision medicine, with the promise of potentially curative, well tolerated, therapies. Targeted Therapy in Translational Cancer Research was written to increase the awareness and access of basic and clinical researchers, caregivers, and patients alike to cutting-edge “bench to bedside and back” breakthroughs, which have transformed the diagnosis, prognosis, and treatment of cancer.

The expert editor team and contributing authors provide an insightful overview to the novel therapeutic approaches targeting the molecular basis of cancer and allowing for the growth of precision medicine. This title is an essential resource for clinical and research oncologists and trainees, pharmacologic research and development professionals, biomedical scientists, and allied oncology professionals.

Translational Oncology Series
Series Editors
ROBERT C. BAST, MD
Vice President for Translational Research
The University of Texas MD Anderson Cancer Center
Houston, TX, USA

MAURIE MARKMAN, MD
Senior Vice President for Clinical Affairs
Cancer Treatment Centers of America
Clinical Professor of Medicine
Drexel University College of Medicine
Philadelphia, PA, USA

ERNEST HAWK, MD, MPH
Vice President, Division of OVP, Cancer Prevention and Population Sciences
The University of Texas MD Anderson Cancer Center
Houston, TX, USA

Other volumes in the Translational Oncology Series
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