Tumor physiology and cell kinetics.
The abnormal physiological state of tumors has traditionally been thought to be a source of treatment resistance and altered metastatic phenotype. However, the recent recognition that this altered physiological state is unique to solid cancers gives some hope that tumor selective therapeutic strategies could be developed that will specifically target these cells. Investigations into the development of drugs that specifically target acidotic and hypoxic cells could represent a significantly selective adjuvant therapy to be used in combination with more traditional forms of treatment. Newer forms of targeted therapy will rely on delivery of directed antibodies, growth factor receptor ligands, or gene therapy, delivered via immune cells or viruses. Unfortunately, physiological barriers exist in tumors that will impede the success of such strategies no matter how specific they are. Methods to ameliorate high interstitial pressures and defects in adhesion molecule function are needed to circumvent these barriers. Current methods of evaluating tumor cell kinetics provide data quickly, so this information could impact treatment decisions. Kinetic parameters are proving to be useful tools in selecting patient subpopulations that may respond better to altered treatment regimens. Studies in spontaneous rodent and xenografted human tumors have shown that the number of clonogens per tumor and their intrinsic sensitivity to radiation are major determinants of radiation tumor control dose.
Dewhirst, MW; LaRue, SM; Gerweck, L
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