TY - JOUR
T1 - Impact, mechanisms, and novel chemotherapy strategies for overcoming resistance to anthracyclines and taxanes in metastatic breast cancer
AU - Perez, Edith A.
PY - 2009/3
Y1 - 2009/3
N2 - Despite advances in treatment of patients with metastatic breast cancer (MBC), prognosis remains poor and median survival is 2-3 years. Resistance to antineoplastics mediated by many factors, potentially including overexpression of drug efflux proteins or altered β-tubulin isotype expression limits the effectiveness of MBC chemotherapy. Capecitabine, approved for anthracycline- and taxane-resistant MBC, has produced modest responses, highlighting the need for more effective treatments for MBC resistant to multiple chemotherapeutic agents. Agents with potential to reverse drug resistance have not proven effective. Albumin-bound paclitaxel is a formulation that may enhance delivery to tumor tissues. Conversely, ixabepilone, an epothilone analog, has been reported to have lower susceptibility to at least some mechanisms of tumor resistance and clinical activity in resistant/refractory MBC. The topoisomerase-I inhibitor irinotecan also has low cross-resistance with other antineoplastics, and has shown some activity against refractory MBC. Development of new agents and identification of genetic biomarkers in translational studies promise to improve management of patients with resistant/refractory breast cancer.
AB - Despite advances in treatment of patients with metastatic breast cancer (MBC), prognosis remains poor and median survival is 2-3 years. Resistance to antineoplastics mediated by many factors, potentially including overexpression of drug efflux proteins or altered β-tubulin isotype expression limits the effectiveness of MBC chemotherapy. Capecitabine, approved for anthracycline- and taxane-resistant MBC, has produced modest responses, highlighting the need for more effective treatments for MBC resistant to multiple chemotherapeutic agents. Agents with potential to reverse drug resistance have not proven effective. Albumin-bound paclitaxel is a formulation that may enhance delivery to tumor tissues. Conversely, ixabepilone, an epothilone analog, has been reported to have lower susceptibility to at least some mechanisms of tumor resistance and clinical activity in resistant/refractory MBC. The topoisomerase-I inhibitor irinotecan also has low cross-resistance with other antineoplastics, and has shown some activity against refractory MBC. Development of new agents and identification of genetic biomarkers in translational studies promise to improve management of patients with resistant/refractory breast cancer.
KW - Chemotherapy-resistant
KW - Drug efflux proteins
KW - Ixabepilone
KW - Metastatic breast cancer
KW - P-gp
KW - β-Tubulin
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U2 - 10.1007/s10549-008-0005-6
DO - 10.1007/s10549-008-0005-6
M3 - Review article
C2 - 18443902
AN - SCOPUS:59449102796
SN - 0167-6806
VL - 114
SP - 195
EP - 201
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -