Poster Presentation at the Third Annual Comprehensive Cancer Management Conference, Washington, DC June 2000
Primary Breast Conserving Treatment for Breast Cancer Using Biologic Response Modification with Insulin in Combination with Non-Toxic Low-Dose Chemotherapy.
Steven G. Ayre, M.D.
ABSTRACT: Cancer chemotherapy drugs are powerful and effective cell-killing agents. Drawbacks to their acceptability by patients and physicians alike are the many side effects of these drugs. Chemotherapy side effects are a function of the high doses required for adequate intracellular dose intensity, plus an inability to target drugs with tissue specificity.
The molecular biology of breast and other cancers involves secretion of insulin and related compounds, along with elaboration of receptors for these ligands. Insulin and the insulin-like growth factors (IGFs) provide cancer cells with autonomous mechanisms for obtaining their fuel (glucose) and for stimulating their growth, respectively.
These mechanisms of malignancy operate via an excess – relative to normal tissues within the host – of insulin and IGF receptors on cancer cell membranes. Using exogenous insulin as a biologic response modifier to take advantage of this property of cancer cells – their high concentration of insulin and IGF receptors – it is possible to profoundly alter cancer chemotherapy pharmacodynamics. As ligand effect is a function of receptor concentration, the interaction of insulin with the excess insulin sensitive receptors on cancer cell membranes effectively differentiates these cells from normal cells within the host.
Moreover, the selective effects insulin has on the cancer cell population are ideal for the potentiation of chemotherapy drug actions. Insulin interacts with cancer cell membrane insulin receptors, altering cell membrane permeability so that lowered doses of chemotherapy agents may be used to generate a more effective intracellular dose intensity. Acting in synergy with this increased intracellular dose intensity is an effect of insulin, by cross-reacting with the IGF receptors, to increase the S phase fraction and render more of the cancer cell population susceptible to actions of commonly used cell cycle phase-specific anticancer drugs.
The combination of lowered total doses of drugs used, plus the targeting of chemotherapy predominantly to cancer cells, reduces anticancer drug side effects significantly, and often completely. Complete tumor responses are observed in most subjects with early diagnosis. Transient hypoglycemic effects of insulin are managed with intravenous hypertonic dextrose. Illustrative cases are presented. This intelligent chemohormonal strategy truly represents a renaissance in cancer chemotherapy.
It is an important advance for Medicine, for the medical industry, and for women diagnosed with breast cancer who wish to preserve all the markers of their feminine identity.