Heat Shock Proteins and Molecular Markers to Predict the Response to Hormone Therapy, Chemotherapy and Radiotherapy

DANIEL R. CIOCCA; LAURA M. VARGAS ROIG; SILVINA B. NADIN

Saint Louis, Missouri, USA

Congreso; 9th International Congress on Hyperthermic Oncology; 2004

During the process of carcinogenesis there is a complex array of mutant and non-mutant gene/protein alterations, these modifications together with the changes in the oxygen levels, nutrients, pH, and drugs/radiation exposures trigger in the cancer cells a stress response including the heat shock proteins (Hsps). Then, the Hsps acting as molecular chaperones are implicated in crucial steps of cancer pathogenesis: proliferation, differentiation, tumor cell recognition by the immune system, invasion/metastasis and death. At the end we have a unique cancer tissue (many times with mixed cancer clones), with a unique molecular milieu which may dramatically change the Hsp context and behaviour. Therefore, several studies have been performed to explore the diagnostic, prognostic, predictive, and treatment implications of the Hsps in several types of human cancers. More specifically, there are studies exploring the utility of the Hsps to predict the response (or lack of response) of a set of cancer patients to a specific treatment(s). This is a very important issue, for example, usually the clinical oncologists provide the treatment based on a list of first line cytotoxic drugs, and then if the disease recurs they go to the second line and so on. A more rational approach  is coming with the finding of molecular markers that predict the response of a cancer type to a specific treatment. The first molecular markers introduced in clinical practice to guide a specific treatment was the determination of estrogen receptors (ERs) in breast cancer patients, ER+ and /or PR+ patients receive hormone therapy. Hsps have been studied as molecular markers to predict the response to hormone therapy, chemotherapy and radiotherapy. During this presentation we will update the progress done in this important field, and present our data regarding the involvement of the Hsps in drug resistance and in helping to predict the response of cancer patients to specific treatments. These studies have been performed on serial breast cancer biopsies by immunohistochemistry and in perypheral blood lymphocytes from pediatric cancer patients by the comet assay.