Topic Subtopic “Pure intellectual stimulation that can be popped into Better Living Health & Wellness the [audio or video player] anytime.” —Harvard Magazine W What Science Knows “Passionate, erudite, living legend lecturers. Academia’s h best lecturers are being captured on tape.” a t —The Los Angeles Times S about Cancer c i e n “A serious force in American education.” c e —The Wall Street Journal K Course Guidebook n o w s a b o u Professor David Sadava t C City of Hope Medical Center and The Claremont Colleges a n c e r Professor David Sadava is Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center. He also is the Pritzker Family Foundation Professor of Biology, Emeritus, at Claremont McKenna, Pitzer, and Scripps, three of The Claremont Colleges. At Claremont, he has twice won the Huntoon Award for superior teaching. Professor Sadava is the author or coauthor of more than 55 peer-reviewed scientific research papers and five books, including two recent biology textbooks. He received his Ph.D. in Biology from the University of California, San Diego. THE GREAT COURSES® Corporate Headquarters 4840 Westfields Boulevard, Suite 500 Chantilly, VA 20151-2299 G USA u Phone: 1-800-832-2412 id e www.thegreatcourses.com b o Cover Image: © Don Farrall/Photographer’s Choice RF/Getty Images. o Course No. 1956 © 2013 The Teaching Company. PB1956A k PUBLISHED BY: THE GREAT COURSES Corporate Headquarters 4840 Westfi elds Boulevard, Suite 500 Chantilly, Virginia 20151-2299 Phone: 1-800-832-2412 Fax: 703-378-3819 www.thegreatcourses.com Copyright © The Teaching Company, 2013 Printed in the United States of America This book is in copyright. All rights reserved. Without limiting the rights under copyright reserved above, no part of this publication may be reproduced, stored in or introduced into a retrieval system, or transmitted, in any form, or by any means (electronic, mechanical, photocopying, recording, or otherwise), without the prior written permission of The Teaching Company. David Sadava, Ph.D. Adjunct Professor of Cancer Cell Biology and Pritzker Family Foundation Professor of Biology, Emeritus City of Hope Medical Center and The Claremont Colleges P rofessor David Sadava is Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center. He also is the Pritzker Family Foundation Professor of Biology, Emeritus, at Claremont McKenna, Pitzer, and Scripps, three of The Claremont Colleges. Professor Sadava graduated from Carleton University as the science medalist, earning a B.Sc. with fi rst-class honors in Biology and Chemistry. A Woodrow Wilson Fellow, he received a Ph.D. in Biology from the University of California, San Diego. Following postdoctoral research at the Scripps Institution of Oceanography, Professor Sadava joined the faculty at Claremont, where he twice won the Huntoon Award for superior teaching, in addition to receiving numerous other faculty honors. He has taught undergraduate courses in general biology and biotechnology and one of the fi rst advanced undergraduate courses in cancer biology. He also has been a visiting professor at the University of Colorado and at the California Institute of Technology. Professor Sadava has held numerous research grants and has written more than 55 peer-reviewed scientifi c research papers, many with his undergraduate students as coauthors. A laboratory scientist, his research concerns resistance to chemotherapy in human lung cancer, with a view to developing new plant-based medicines to treat this disease. He is the author or coauthor of fi ve books, including the recently published ninth edition of a leading biology textbook, Life: The Science of Biology, as well as a new biology textbook, Principles of Life. i Professor Sadava also has produced Understanding Genetics: DNA, Genes, and Their Real-World Applications with The Great Courses. ■ iiii Table of Contents INTRODUCTION Professor Biography ............................................................................i Course Scope .....................................................................................1 LECTURE GUIDES LECTURE 1 Cancer Is an Ongoing Challenge .......................................................5 LECTURE 2 Cancer Is a Major Burden to Society ................................................12 LECTURE 3 Discovering Causes of Cancer in Populations .................................18 LECTURE 4 Some Causes of Cancer in Populations ...........................................25 LECTURE 5 DNA Is the Key to Understanding Cancer ........................................31 LECTURE 6 How Does DNA Change to Initiate Cancer? .....................................38 LECTURE 7 How Do We Know If Something Causes Cancer? ...........................44 LECTURE 8 How Do Normal Cells Function? ......................................................50 LECTURE 9 What Is Different about Cancer Cells? .............................................56 LECTURE 10 How Do Tumors Grow? ....................................................................63 iii Table of Contents LECTURE 11 How Tumors Spread and Thrive .......................................................69 LECTURE 12 What Are Tumor Viruses? .................................................................75 LECTURE 13 How Do Tumor Viruses Cause Cancer? ...........................................81 LECTURE 14 How Do Cancer-Causing Genes Work? ...........................................87 LECTURE 15 Can Cancer Be Inherited? ................................................................93 LECTURE 16 How Do Normal Genes Suppress Tumors? .....................................99 LECTURE 17 How Do Genetic Changes Result in Cancer? ................................105 LECTURE 18 Treating Cancer with Surgery .........................................................111 LECTURE 19 Treating Cancer with Radiation ......................................................117 LECTURE 20 Treating Cancer with Drugs ............................................................123 LECTURE 21 How Do Drugs Attack Cancer? .......................................................129 LECTURE 22 Frontiers of Cancer Treatment........................................................135 LECTURE 23 Can Screening for Cancer Be Useful? ...........................................141 iivv Table of Contents LECTURE 24 Can Cancer Be Prevented?............................................................147 SUPPLEMENTAL MATERIAL Glossary .........................................................................................153 Bibliography ....................................................................................163 v vvii What Science Knows about Cancer Scope: T here are few words in any language that strike as much fear as the word “cancer.” One person in three develops malignant cancer in his or her lifetime, and one out of four dies from it. The aim of this course is to explain the science that underlies this disease. As you learn about how cancer works to subvert the body’s normal functioning, you will see how cancer can be treated and even prevented. The fi rst part of the course sets the stage, describing the challenge that cancer poses to humanity. Lectures 1 and 2 outline where we have been and where we are. Because cancer typically strikes older people, it was relatively rare until the past century. People thought—and many still think—that cancer was caused by an imbalance of bodily fl uids or was a punishment by a deity. More recently, explanations of cancer based on the chemistry and physics of cells in the body have taken hold. The U.S. government optimistically declared a 10-year “war on cancer” in 1972. Clearly, it failed and has turned into a war of attrition. After heart disease, cancer is still the second leading cause of death, with lung cancer leading the way. Lectures 3 and 4 deal with epidemiology, the study of diseases in populations. It seems that every day, the results of long-term studies of groups of people point to new links between diet, environmental exposure, or lifestyle and cancer. The most obvious of these culprits is tobacco smoking, which is implicated in about one-third of all cancer. Less clear are the effects of various aspects of diet, where data are often confl icting. Even less clear is the link between personality and cancer. More direct information on the causes of cancer is revealed in the second part of the course. In Lecture 5, we enter the cell and focus on its genetic material, DNA. This is where a lot of cancer begins. The human genome has several billion chemical “beads” making up long chains of DNA in every one of the trillions of cells in the body. Many of the instructions in DNA are expressed as proteins. Mutations are changes in the DNA “beads.” Every day, thousands of these changes occur spontaneously in many cells, and they 11 can result in altered proteins with changes in cell functions. As Lecture 6 points out, most cancer-causing agents (carcinogens) cause mutations in DNA. We are exposed to thousands of these agents all the time, ranging from ultraviolet radiation from the Sun, to naturally occurring chemicals in the bodies of plants and animals that we eat, to industrial pollutants. Cells have ways to repair the DNA mutations before cancer starts. But too often, the damage overwhelms the repair systems, and the mutations are permanent. Lecture 7 describes how scientists have developed lab tests on simple organisms to try to sort out cancer-causing agents from harmless ones. Unfortunately, the results of these tests are often unclear and may not apply to humans—so people and governments apply risk analysis, where costs and benefi ts of exposure are weighed and decisions are made. The third part of the course describes the features of cancer as a disease of cells. In Lectures 8 and 9, cells in general and cancer cells in particular are introduced. All cells in the body—whether on the skin or inside the heart—have basically the same overall structure, with the entire DNA genome enclosed in a nucleus. When a cell’s DNA is changed, its functions can change, and cancer can be initiated. This results in cell changes such as constant cell reproduction (so that the tumor grows); changes in the cell surface (so that cancer cells are less “sticky”); and a general dedifferentiation, or loss of specialized appearance and function. While a tumor with billions of cells may arise from a single cell, the cells keep on changing so that only some of the cells may retain the ability to keep growing. These are called cancer stem cells. In Lectures 10 and 11, the growth and spread of cancer are described in cellular terms. Tumors can be benign or malignant. Benign tumors grow to a limited size and typically stop as a ball of cells; they do not spread but can cause signifi cant illness when they grow inside an organ such as the brain. Malignant tumors can metastasize, or spread by breaking off some cells and sending them throughout the body via the blood or lymphatic systems. Tumors send chemical signals to nearby blood vessels to sprout branches to nourish the tumor, a process called angiogenesis. As a tumor grows and spreads unchecked, it places an increasing burden on the body’s functions, leading to serious illness and death. e p The fourth part of the course describes the scientifi c discoveries about o c S cancer deep inside cells. Some of these have come from cancer viruses and 2