Resistance to Targeted Therapies in Lymphomas

Over the past few decades, lymphoma patient outcomes have improved as a result of multidrug chemotherapy and radiation therapy, intensification of treatment, improvement in supportive care, and better imaging and staging systems. Even more recently, there has been tremendous progress in the understanding of cancer cell biology and its microenvironment which has resulted in the development of biologic agents, also called "target" therapies. These therapies are more specific in targeting cancer cells either directly or via enhancement of the immune system. Many clinical studies have focused on biological agents in combination with traditional chemotherapy with the goal of improved outcomes, or reduced acute long term complications that are associated with lymphoma therapy.

This volume will review different classes of "target" drugs that have been developed, approved, or are under investigation in the field of lymphoma therapy. The discussion will not only be on the understanding of the mechanisms of action or clinical response of those agents, but will also help the reader to understand the nature of lymphoma biology in patients who relapse or are refractor after exposure to those drugs.

Contributors will discuss what is currently known about mechanisms of tumor-related or host-related resistance, and how to overcome this resistance. This understanding is crucial given the dismal outcomes of patients with relapsed or refractory lymphomas. The book provides a unique opportunity to review and reflect on the recent successes and pitfalls of the modern lymphoma therapy era.

Dr. Ana C. Xavier is an Associate Professor at the Division of Hematology/Oncology, Department of Pediatrics at the University of Alabama at Birmingham (Birmingham, Alabama). She received her medical degree from the University of Sao Paulo, Brazil. She completed her pediatric residency at the Medical University of South Carolina and Pediatric Hematology/Oncology fellowship training at the Wayne State University. Dr Xavier is board certified in Pediatrics and Pediatric Hematology/Oncology and currently serves as Associate Program Director of the Pediatric Hematology/Oncology Fellowship Program at the University of Alabama at Birmingham. She has authored numerous peer-reviewed manuscripts in highly reputed international journals and has presented several abstracts at various national and international conferences. She holds memberships with the American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology and Children's Oncology Group. Dr. Xavier's clinical practice includes both pediatric oncology and her research interest focus on the treatment of pediatric patients with lymphoma.

Mitchell S. Cairo is currently the Associate Chairman and Professor (with tenure) in the Department of Pediatrics at New York Medical College (NYMC). His additional current leadership positions include being the Chief of the Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Program Director of the Adult & Pediatric BMT Program, Director of the Childhood and Adolescent Cancer and Blood Disease Center, Medical and Scientific Director of the GMP Cellular and Tissue Engineering Laboratory at Westchester Medical Center (WMC), Medical Director of the WMC Hematotherapy Program and Co-Chair of the WMC Cancer Committee. Dr. Cairo's additional academic appointments include being a Professor of Medicine, Pathology, Microbiology and Immunology and Cell Biology and Anatomy and Public Health at NYMC. Briefly, Dr. Cairo's past education includes his undergraduate studies at the University of Wisconsin, Madison, WI, graduating in 1972 with a BA and election to Phi Beta Kappa. Dr. Cairo received his medical school training at the University of California, San Francisco (USCF) graduating in 1976 and election to Alpha Omega Alpha (AOA). Dr. Cairo trained as a Pediatric Resident at UCLA Harbor General from 1976-1978 under the mentorship of Joseph St. Geme, MD and then a Chief Residency in Pediatrics from 1978-1979 at UCSF under the mentorship of Melvin Grumbach, MD. Dr. Cairo completed a Pediatric Hematology-Oncology Fellowship as an American Cancer Society Fellow at Indiana University from 1979-1981 under the mentorship of Robert Baehner, MD. Dr. Cairo joined the faculty of Children's Hospital of Orange County (CHOC) in 1982 and established the BMT/Stem Cell Transplant program there in 1985 as Director of Blood and Marrow Transplantation. Also, at CHOC Dr. Cairo wasthe Principal Investigator (PI) for Children's Cancer Group and PI of the Cord Blood Collection Center and Cord Blood Transplant Center under an NHLBI award. In 1997, Dr. Cairo was recruited to Georgetown University where he became a Professor of Pediatrics, Medicine and Pathology and Chief of the Division of Stem Cell Transplantation, Cellular and Gene Therapy and Director of the Adult and Pediatric Bone Marrow Transplantation program at the Lombardi Cancer Center and Medical Director of the NHLBI Cord Blood Collection Center and Cord Blood Bank. In 2000, Dr. Cairo was recruited to Columbia University and was a Professor of Pediatrics, Medicine and Pathology and Director of the Division of Blood and Marrow Transplantation, member of the executive committee of the Department of Pediatrics, Medical Director of the National Marrow Donor Unrelated Transplant program, Chief of the Division of Pediatric Blood and Marrow Transplantation and member of the executive steering committee of theMorgan Stanley Children's Hospital of NewYork-Presbyterian Hospital. In 2011 Dr. Cairo was recruited to NYMC and WMC. Dr. Cairo has over 410 peer reviewed publications, over 1200 national and international abstract presentations, over 50 book chapters and edited 2 textbooks. Dr. Cairo is on the editorial board of British Journal of Hematology, Blood Reviews, Cell Transplantation and past editorial board member of Bone Marrow Transplantation and Experimental Hematology. Dr. Cairo is a regular NCI reviewer for PPG and Spore applications. Dr. Cairo has been a member of the CCG/COG Bone Marrow Transplantation, now Cell Therapy Committee for the last 20 years. Dr. Cairo was the chair of the ISCT Immuno-Gene Therapy Committee and currently is the ISCT North America Vice President Elect and past Co-Chair of the CIBMTR Cellular Therapy Committee. Dr. Cairo is also a long standing member of the PBMTC Executive and Steering Committee. Dr. Cairo is an international leader in the biology and treatment of childhood and adolescent lymphomas and leukemias, stem cell transplantation, developmental therapeutics, experimental hematopoiesis and immunology, tumor immunology and biology and stem cell biology and regenerative therapy. Dr. Cairo was a pioneer in the use of cord blood stem cells for treating pediatric malignant and non-malignant disease, the use of cord blood stem cells for potential regenerative therapy and haploidentical stem cell transplantation for paients with sickle cell disease. Dr. Cairo is a member of a number of national and international societies related to both pediatrics and Hematology/Oncology/Stem Cell Transplantation, including, elected to the Society of Pediatric Research (SPR) and the American Pediatrics Society (APS) and member of AAP, ESPR and hematology and oncology and stem cell transplantation societies such as ASH, ASCO, ASBMT, CIBMTR, AAI, ISEH, AACR, ASPHO, SIOP, PBMTC and COG. In summary, Dr. Cairo has been aninternational leader in basic, translational and clinical research in childhood, adolescent and young adults with emphasis in stem cell transplantation, stem cell biology, lymphoma, tumor immunology, and developmental therapeutics.