Title:Mechanistic Insight of Drug Resistance with Special Focus on Iron in Estrogen Receptor Positive Breast Cancer
VOLUME: 15 ISSUE: 12
Author(s):Rashmi Mittal, Narender Chaudhry, Shubha Pathania and Tapan K. Mukherjee
Affiliation:Department of Biotechnology, Maharishi Markendeshwar University, Mullana, Haryana-133203, India.
Keywords:Antiestrogens, breast cancer, combinational therapy, drug resistance, estrogens, estrogen receptors.
Abstract:Estrogens along with their receptors are required for the normal physiological development of women. However,
in altered physiological conditions a high level of estrogens acts either as initiator or progressor of breast cancer.
Approximately in 75% of estrogen dependent breast cancer cases estrogen receptors (ERs) are held responsible. Recent
studies indicate that estrogens along with iron (Fe) concomitantly involved in the proliferation of ER+ breast cancer cells.
While a number of antiestrogen/anti-ER drugs including selective estrogen receptor modulators (SERMs), aromatase inhibitors
(AIs) and selective estrogen receptor down regulators (SERDs) are used to eradicate breast cancer but their action
on Fe dependent breast cancer complication is not yet explored. Moreover, many of the ER+ breast cancer patients receiving
anti-estrogen drugs relapsed within a couple of years and become resistant to antiestrogen therapy. Mutation and loss
of affinity to the target molecule (ERs), loss or overexpression of ERs, along with activation of growth promoting pathways
alternative to estrogen-ER pathways are the major reasons of drug resistance. Combinational therapy may be best alternative
to antiestrogen relapsed patients. Some of the widely studied drug combinations are roscovitine (ROSC) and tamoxifen,
metformin and tamoxifen, tamoxifen and RAD001. While in all these drug combinations anti-ER compound tamoxifen
may be one of the major content, anti-Fe compounds are yet to be used as drug combination. The present review
article describes all the currently studied drugs/drug combinations in ER+ breast cancer cells and future drug possibilities
including anti-Fe compounds.
