Among the highlights in the December 1999 Cancer Watch issue are: Multidrug Resistance by Hyperthermia, Proliferating Cell Nuclar Antigen (PCNA), A New Candidate Tumor Suppressor Gene, p73, Cancer risks in BRCA2 Mutation Carriers, Advances in the Treatmnet of Colorectal Cancer, Advances in the Treatmnet of Colorectal Cancer, Radiation and Chemotherapy Combination for Cervical Cancer, Ceramide Synthase Reverses Radiation Resistance in Prostate Cancer Cell, Immunotherapeutic Approaches Hopeful for Non-Hodgkin's Lymphoma Patients, Cancer Patients Respond to Immunotoxins, Ribozymes as a Technology Tool, The Benefits of Cancer Screening, New Atlas of Cancer Mortality.

• Current developments in cancer biology and treatment such as gene therapy.

• Circumvention of multidrug resistance by hyperthermia
• Cancer-specific "proliferating cell nuclar antigen (PCNA)
• A new candidate tumor suppressor gene, p73
• Cancer risks in BRCA2 mutation carriers
• Advances in Testing Gene Expression

• For almost four decades, there has been little progress in the systemic treatment of colorectal cancer after surgery. Traditionally, 5-fluorouracil (5-FU) has been the treatment of choice, with little effect on overall survival or the resulting quality of life. It is only during the last five years, with the rapidly increased understanding of cancer biology, significant advances are being made: genetic markers are expected to allow for improved selection of responders to therapy, new cellular targets are being identified with novel cytostatic drugs directed against them. A brief review of major, novel agents recently introduced for the treatment of colorectal cancer follows, based on reports from the team of J. L. Marshall, at the Lombardi Cancer Center, Georgetown University, Washington, DC.

• The p53 protein is a critical player in regulating cellular growth and stress responses, and in maintaining genomic stability. Mice lacking the Gadd45a gene mimic several of the phenotypic characteristics of loss of p53 function, including genomic instability and increased radiation carcinogenesis. Hence, Gadd45a represents an important component of the p53 pathway, enabling it to function as an effective tumor suppressor and genome guardian.

• Mitomycin C, a chemotherapeutic agent, that specifically kills cells at low oxygen levels, has beneficial effect in locally advanced cervical cancer patients when given in combination with radiation.
  

• Radiation resistant prostate cancer cells can be made sensitive by pretreating with an agent that activates an enzyme to synthesize ceramide. Ceramide signals a specific apoptotic pathway.
  

• While a number of treatment options are possible for patients with low grade, follicular non-Hodgkin's lymphoma (NHL), monoclonal antibody therapy is the most exciting new strategy on the horizon, according to several scientists, speaking at the 4th Annual Patient Educational Forum on Lymphoma..

• Hairy-cell leukemia patients responded very well to a second generation of trimmed recombinant immunotoxin after failure in chemotherapy.

• Ribozyme, an RNA enzyme can be engineered in such a way that it interacts with a specific mRNA molecule in sequence-dependent fashion and cleaves it. This inhibits the translation of RNA to protein, thus preventing the expression of a specific gene. The technology could be used to identify therapeutic target genes and ribozymes can thus be used in gene therapy.

• The ethical aspects are simple and clear: any reasonable, non-invasive measures which detect cancer and thus improve life quality or expectancy should not be denied to the general population. It is self-evident that screening must be harmless in itself, reliable (sufficiently, but not excessively sensitive) and that the malignant growth detected can be treated with some degree of success. It must always be kept in mind that cancer has a characteristic, very individual course, with unknown periods of latency and spontaneous (?) transient remissions; earlier diagnosis may only prolong life as an actuarial artefact. Finally, whether we like it or not, economic restrictions will eventually rise their ugly head and influence decisions which may not be in the patient’s best interests.

• A glossary of unfamiliar words and jargons in Cancer Watch, December '99.