Cancer: Blueprint of a Tumor
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Scientists are deciphering the biology of the tumor cell at a level of detail that would have been hard to imagine just a decade or so ago. The development of high-throughput DNA sequencing and genomics technologies have allowed an understanding of the development, growth, survival, and spread of cancer cells in the body. From this information, we now have a basic blueprint or roadmap of how a single damaged cell can develop into a pre-malignant lesion, a primary tumor, and finally, a lethal tumor that may spread throughout the body and resist both medical therapy and host immune responses. In this book, we provide an overview of our current understanding of this cancer blueprint, which has been aided both by the study of familial cancer syndromes, in vitro studies of cancer cells, and animal models. Three classes of genes have emerged from these studies: tumor suppressor genes needed for normal growth control and DNA repair; oncogenes that regulate cell growth and survival, and epigenetic modifiers, enzymes that regulate the modification of DNA and the proteins that form chromatin. Each of these three classes of genes is mutated or altered at least once in virtually all malignant cancer cells. Current technologies permit the DNA sequencing of cancer exomes (coding gene sequencing), whole genomes, transcriptome (all expressed genes), and DNA methylation profiling. These studies show that all tumors have unique constellations of mutated, rearranged, amplified, and deleted genes. Single-cell sequencing further shows that there is extensive variation in individual cells in the tumor; that cancers evolve, and have many of the properties of a multi-cellular entity. Lastly, cancer cells, through mutations in epigenetic modifiers, can reprogram the genome and unlock entire developmental and gene expression pathways to adapt and survive in changing conditions. This reprogramming allows the tumor to elude the host body's defenses, radiotherapy, chemotherapy, and targeted therapy that we use in cancer treatment. Understanding this cancer blueprint paves the way for the development of future therapies to treat and eliminate cancer.
Dean, Michael: -
Dr. Michael Dean obtained his Ph.D. from the Biochemistry Department at the Boston University School of Medicine. He performed his postdoctoral studies at the National Cancer Institute on the MET oncogene and the cystic fibrosis gene, and he is currently the Chief of the Laboratory of Translational Genomics at the National Cancer Institute.
Dr. Dean has published more than 200 research articles in peer-reviewed journals including Nature, Science, Cell, and the New England Journal of Medicine. In addition, he has authored numerous review articles and chapters in journals and books including those for the public, such as Scientific American, Nature Reviews, and Discovery Medicine. He is a member of the American Society of Human Genetics, Centre Etude du Polymorphisme Humaine (CEPH), the Human Genome Organization (HUGO), and an adjunct faculty member at Hood College.
Dr. Dean is the recipient of the Young Investigator Award from the American Association for Cancer Research and the National Institute of Health Director's Award. He holds more than 12 patents for the discovery of human disease genes.
Dr. Dean's current research interests include the genetic analysis of complex disease, genetic variation in human tumors, ABC transporters, age-related macular degeneration (AMD), and cancer stem cells. He is also actively involved in pediatric cancer research efforts in Latin America, including studies of childhood leukemia, retinoblastoma, cervical cancer, and health disparities among indigenous Mayan people of Guatemala.
Moitra, Karobi: - Dr. Karobi Moitra is a Clare Boothe Luce Assistant Professor of Molecular Biology at Trinity Washington University in Washington, DC. She received her Ph.D. in Zoology from the University of Burdwan in India. Dr. Moitra relocated to the United States and trained in Biochemistry and Molecular Biology at the Uniformed Services University of the Health Sciences in Bethesda, MD, and at the Frederick National Laboratory for Cancer Research (Frederick, MD). She has received the Fellows Award for Research Excellence from the NIH for her research centered on the role of ABC transporters in human disease and drug resistance. Dr. Moitra has authored numerous scientific papers and two textbooks. Dr. Moitra is dedicated to educational outreach and in training and mentoring students. At Trinity, she teaches Introductory Genetics, Cell and Molecular Biology, Evolution, and Critical Thinking About Disease and has received outstanding evaluations from her students. Dr. Moitra also enjoys writing fiction and has contributed her writing to the Human Genre Project. She has recently taken an active interest in Educational Research and particularly in the art of storytelling as an educational tool in the sciences. Outside of the classroom and laboratory, she enjoys reading, cooking, traveling, and has started a new hobby--creating artwork based on science.
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