Cancers as Systemic Eunctional Diseases, Part 2: Clinical Implications

T he emerging view is that many cancers, due to present therapeutics, may become chronic diseases that need to be managed over many years with diet, lifestyle, and environment changes.'-^ Management of the patient that is appropriate for the stage of his or her disease is dependent upon the availability of biomarkers or screening tests that have been validated to define the status ofthe individual. Traditionally, four types of screening tests have been employed, including early-detection screening such as the Pap test, mammography, dermatology screen, oral screen, and colonoscopy. The second type of screening is the use of gene-based cellular tumor-specific markers such as KRAS, the APC gene, TP53 and BAT26 in stool sample DNA, or cytological examination of cells in sputum samples. The third type of screening test is the use of serum or urine genetic markers including cyclin E, MCM, PCNA, pl6, BCL-2, and VEGF that monitor cell-cycle progression, DNA replication, DNA synthesis, cell-cycle control, antiapoptosis, and angiogenesis. One prime example of this is the use of CA-125 as a tumor marker for women with ovarian cancer. The fourth type of screening test employs soluble serum or urine metabolites to follow the course of disease such as the use of catecholamine metabolites such as vanillylmandelic acid (VMA) and homovanillic acid (HVA) in the urine of patients with neuroblastoma. Genetic and molecular biological screening tests traditionally have been used in following the course of therapy in a well-described form of cancer. Beyond these traditional approaches to cancer assessment, however, is emerging another strategy for the assessment ofthe fimctional state ofthe patient's physiology that is related to both his individual predisposition to cancer as well as the design of a personalized program for the chronic management of the cancer survivor. This type of biomarker screening takes its lead fi-om the pioneering work done on the value of prostate-specific antigen (PSA) screening in males for defining the risk and progression of prostate cancer,'" The states of cancer fi-om initiation through promotion and progression have different stages of disturbed metabolism associated with them. There are biomarkers that identify these stages of distorted physiology and reflect the state of fiinction that is consistent with cancer. These stages of disturbed physiology include