Multidrug Resistance in Breast Cancer: Occurrence and Therapeutic Implications.
Annual rept. 1 Oct 96-30 Sep 97,
UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
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Though clinical development of drug resistance during treatment of breast cancer has been apparent for at least two decades, little known about the mechanisms involved. Multidrug resistance mdr mediated by the MDRI gene expression is one of multiple factors identified which may be associated with declining therapeutic efficacy anticancer drugs after failure of an initial therapy. This research program seeks to define MDRI expression clinical specimens, and its relationship to age, menopausal status, stage, hormone receptors, site of disease, an prior treatment Through clearly defined and clinical protocols, it will also correlate drug treatment breast cancer to the expression and function of MDRI and its P-glycoptrorein Pgp. Clinical specimens fro primary or metastatic breast cancer patients are tested for MI expression by Polymerase Chain Reaction PcR and by immunostaining for Pgp with monoclonal antibodies. These analyses are also applied to patients enrolled in a series of therapeutic studies including paclitaxed Taxol in patients having failed other therapies. Preliminary expression analysis of other potentially important genes, such as p53 tumor suppressor gene and p7 is in progress Response to treatment and findings are correlated. In patients exhibiting resistance to Taxol, strategics involving resistance-reversal through dose-scheduling and resistance-modifiers are being developed randomized Phase II trial of Taxol without and with resistance modifiers is in progress. The composite of these studies will provide information defining the importance of multidrug resistance in determining the outcome fro systematic taxol therapy in the treatment of breast cancer.
- Medicine and Medical Research