The goal of cancer research is to understand how cancer can be prevented and to develop cures for every type of cancer. The recognition that cancer is fundamentally a genetic disease has opened enormous new opportunities for preventing and treating it. Carcinogens can now be assessed for their effects on known steps in the loss of genomic integrity. Genetic defects in the checkpoint pathways for detecting damaged DNA and in the systems for repairing it can be readily recognized and used to explore the mechanisms of cancer. The multiple changes that must occur for a cell to grow into a dangerous tumor present multiple opportunities for intervention. The genomic revolution has provided the tools needed to identify every genetic alteration driving tumorigenesis, thereby providing targets for therapeutic interventions.
Diagnostic medicine is being transformed by our newfound ability to monitor large numbers of cell characteristics and by ever more sensitive methods of detecting smaller numbers of tumor cells. The traditional methods of assessing possible tumor cells—
The molecular cell biology of cancer provides avenues for new therapies, but prevention remains crucial and preferable to therapy. Avoidance of obvious carcinogens, particularly cigarette smoke, can significantly reduce the incidence of lung cancer and perhaps other kinds of cancer as well. Beyond minimizing exposure to carcinogens such as smoke or sunlight, certain specific approaches to prevention are now feasible. New knowledge of the involvement of human papillomavirus 16 in most cases of cervical cancer led to the development and FDA approval of a vaccine that prevents three-
Understanding the cell biology of cancer is a critical first step toward prevention and cure, but the next steps are hard. The success of Gleevec (imatinib) against leukemia is exceptional. Results such as those seen with RAF inhibitors in melanoma are more typical. The initial response to RAF inhibitors is spectacular, but tumors reappear within a year and are resistant to the treatment. Moreover, for most cancer types, specific therapies are lacking altogether. This “druggability gap” prevents effective treatment of many cancers. Filling it will be the great challenge for the pharmaceutical industry and academic science alike. The understanding that a person’s cancer is not a homogenous disease, but a conglomerate of cells endowed with different characteristics, calls for the development of combination therapies in which all cancer cell populations in a tumor are targeted, preventing relapse after treatment and bringing a lasting cure of the disease. Despite these daunting realities, we are beginning to reap the benefits of decades of research exploring the molecular biology of the cell. We hope that many of the readers of this book will help to overcome the obstacles that remain.