Cancer Medicine

1908 Nobel Laureate in Medicine, Paul Ehrlich, a scientist in the fields of hematology, immunology, and chemotherapy, first coined the medical term chemotherapy (Thorburn, 1983).  This father of immunology and pioneer of chemotherapy’s work with the use of rodent models of infectious disease, to develop antimicrobial agents, led George Clowes to develop inbred rodent lines carrying transplanted tumors.  These models were subsequently used in the development of cancer chemotherapeutic compounds.  Alkylating agents were the first class of modern chemotherapeutic drugs.  These agents were produced under the secret war program during the first and second world wars (Marshall, 1964, Hersch 1968).  The exposure of mustard gas to seamen as well as an explosion in Bari Harbor during the Second World War led to the association of marrow and lymphoid hypoplasia with alkylating agents (Alexander, 1944).  This subsequently led to the use of these agents in Hodgkin’s disease and lymphocytic lymphomas.  The treatment and cure of leukemia in children as well as Hodgkin’s disease with combination chemotherapy during the 1960s demonstrated that this approach could be used in advanced cancers, which led to its successful and popular employment to date (Devita, 1978).

Cancer is the second leading cause of death in the United States.  In 2008, an estimated 1.47 million new cases of cancer were diagnosed in the United States.  Cancers with the highest fatalities were lung, breast, and prostate.  The leading sites for cancer in males include prostate, lung, colon and rectum with 186,320, 114,690 and 77,250 cases, respectively, expected to have occurred in the United States in 2008.  In females, the leading sites by incidence include breast, lung, colon and rectum, with 182,460, 100,330 and 71,030 cases respectively, occurring in this population, in 2008.  In terms of cancer deaths in 2008 by site and sex, the leading sites for men included lung (90,810 cases), prostate (28,660 cases), and colon and rectum (24,260 cases).  This statistic in females, was as follows: lung (71,030 cases), breast (40,480 cases), and colon and rectum (25,700) cases (Anonymous, 2008).  It may be quite possible to prevent many of these deaths via cancer prevention and screening programs as well as improved access to medical care.  There may also be a disparity in terms of stage per stage presentation of cancer across various populations.  Various treatment and prevention modalities are currently in place.  Treatment approaches include surgery, radiation therapy, and chemotherapy.  Newer approaches include gene therapy, immunotherapy, bone marrow transplantation, and chemotherapy with hematopoietic growth factor support.  Preventive strategies often include environmental, social and dietary modification (Anonymous, 2008, Anonymous, 1998).  Many of the approximately 1 million cases of skin cancer diagnosed in 2008 could have been prevented via protection from sunrays (Anonymous, 2008).  In 2008, the most common form of skin cancer was melanoma, which was diagnosed in approximately 62,480 individuals, with an estimated 8,420 deaths.  Chemoprevention, a novel approach to cancer control, utilizes pharmacologic, nutritional or endocrine mechanisms to inhibit the process of carcinogenesis (Grenwald, 1995, Hong and Sporn, 1997, Krishan, 1998, Dunn, 1998, Thompson, 1997, Wattenberg, 1992).  

Most aspects of natural product drug discovery programs described in this book were conducted at the University of Illinois at Chicago and have been documented in the literature (Gerhäuser, 1995, Udeani, 1997, Kinghorn, 1998).  The experimental approach observed to be most practical for natural product drug discovery is bioassay-directed fractionation.  During this process, starting materials are selected.  This usually involves random collection, information derived from ethnomedical systems of medicine, or literature surveillance, resulting in extracts suitable for biological evaluation being prepared.  These materials are subsequently tested in a bioassay system, and substances indicative of positive response are considered as active leads.  After a number of active leads are obtained, the most promising materials are fractionated.  Each fraction is monitored for potential to mediate a positive response in the bioassay test system, and this process continues until a pure active substance is derived.  The resulting substance is further subjected to procedures of structural elucidation.  As soon as an active isolate is obtained, more thorough biological evaluation procedures are often performed and, based on the accumulated data, the material becomes a candidate for further and advanced testing and development (Pezzuto, 1995).  Such testing includes in vivo carcinogenesis as well as further development - pharmacokinetics and pharmacodynamics (Udeani, et al, 1997, 1999, 2001). The two major categories of drug discovery from natural products explored include (1) chemopreventive agents and (2) chemotherapeutic agents.  Pharmacological interventions remain a mainstay in the treatment of cancer.