Preface

Cancer is a disease that has been in existence throughout the history of the human race. The term “carcinoma” was coined as early as in the fourth century B.C. Cancer is a unique and most feared malady that humankind has ever faced. At present, in technologically developed countries one out of every three individuals will be affected with cancer during his or her lifetime, and the prediction is that this may increase to one in two by the next decade. The last century, particularly the last three decades have witnessed remarkable progress in our understanding of the molecular basis of how cancer cells originate and spread to distant organs. It has now been well established that accumulated mutations of a cascade of specific genes in a single cell are required for a normal cell to become a cancer cell. The aim of this special issue of the Current Molecular Medicine on cancer is to provide comprehensive reviews of a number of key alterations in cell physiology, mentioned below, that collectively are considered to be involved in the genesis of cancer. First, genomic instability in cancer cells is considered to be the primary event by which a single cell may accumulate multiple genetic mutations that allow it to acquire properties that are crucial to become a cancer cell. Almost all cancer cells show abnormalities in chromosome structure and number. Even progenies of a cancer cell do not retain the structural and numerical changes in chromosomes present in the parental cell. Second, normal cells possess intrinsic genetic program that limits their replicative potential and leads to senescence. Cancer cells circumvent senescence and become immortal. Certain genes are up regulated in a tumor cell to sustain its limitless replicative potential. Third, there are a group of genes known as tumor suppressor genes, which normally prevent unscheduled cell division. Mutation or loss of tumor suppressor genes induces uncontrolled division of mutated cells in the body, which may lead to the development of cancer. Fourth, the balance between the generation of new cells and genetically programmed cell death, called apoptosis maintains tissue homeostasis (stability of the organ mass). This apoptotic pathway is disturbed in cancer cells due to mutations of specific genes, causing increased tumor mass. Fifth, as the tumor mass increases, it requires the formation of new blood vessels to supply cells with appropriate nutrients for further growth of the tumor. The sprouting of new vessles from the existing vessles is called angiogenesis. In cancer cells induction and maintenance of such a process occur due to gene mutations which stimulate synthesis of angiogenic factors. Sixth, a cancer cell must acquire the ability to invade surrounding tissues, and penetrate blood and Iymphatic vessels. Which allow the cell to migrate to distant organs. The cancer cell acquires this property by functional elimination of genes that suppress the cell's ability to invade tissues and metastasize. This compilation of reviews should help the reader conceptualize the unique nature of the disease called cancer, and to understand the reason why inspite of the enormous efforts that are being made by researchers worldwide, a cure for cancer has not yet been found. The real problem is when a single cell is converted to a cancer cell and starts dividing in an uncontrolled manner, and its progenies spread all over the body, each and every one of such cells cannot be killed without causing fatal side effects. Based on our present knowledge of cancer at the molecular and cellular levels, attempts are being made by researchers worldwide to try out various approaches to cure cancer. Using such approaches, significant progress has been made in the detection of some cancers at an early and treatable stage. Combination of presently available therapies, customized for specific cancer patients have proved successful in some cases. Improved drugs for chemotherapy, and radiation therapy have prolonged remission time for many cancer patients. However, the development of a magic bullet for curing most invading cancers appears remote at present. The major problem has to do with the fact that once the cancer metastasizes, it is virtually impossible to kill each and every cancer cell in the system, and a single surviving malignant cell may eventually cause the cancer to reappear. This has been the heart of the problem in curing metastasizing cancers, irrespective of the therapies that are presently being used. Thus, it may be more prudent to refocus our research priorities, and direct the bulk of the available research resources to further improve technologies for early detection and implementation of preventive measures to fight cancer. Let us hope that Dr. Robert A. Weinberg is right when he wrote - “One day, we imagine that cancer biology and treatment - at present, a patchwork quilt of cell biology, genetics, histopathology, biochemistry, immunology, and pharmacology - will become a science with a conceptual and logical coherence that rivals that of chemistry or physics.........those researching the cancer problem will be practicing a dramatically different type of science than we have experienced over the past 25 years”.