Estrogen Receptor-β and the Insulin-Like Growth Factor Axis as Potential Therapeutic Targets for Triple-Negative Breast Cancer.
Triple-negative breast cancers (TNBCs) lack estrogen receptor-α (ERα), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) amplification and account for almost half of all breast cancer deaths. This breast cancer subtype largely affects women who are premenopausal, African-American, or have BRCA1/2 mutations. Women with TNBC are plagued with higher rates of distant metastasis that significantly diminish their overall survival and quality of life. Due to their poor response to chemotherapy, patients with TNBC would significantly benefit from development of new targeted therapeutics. Research suggests that the insulin-like growth factor (IGF) family and estrogen receptor beta-1 (ERβ1), due to their roles in metabolism and cellular regulation, might be attractive targets to pursue for TNBC management. Here, we review the current state of the science addressing the roles of ERβ1 and the IGF family in TNBC. Further, the potential benefit of metformin treatment in patients with TNBC as well as areas of therapeutic potential in the IGF-ERβ1 pathway are highlighted.
UCLA School of Nursing, Los Angeles, CA; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA.
Nalo
N
Hamilton
UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA; Department of Medicine, Division of Hematology-Oncology, UCLA David Geffen School of Medicine, Los Angeles, CA.
Diana
D
Marquez-Garban
Department of Human Genetics, University of California at Los Angeles, Los Angeles, CA 90095; Department of Medicine, Division of Hematology-Oncology, UCLA David Geffen School of Medicine, Los Angeles, CA.
Vei H
VH
Mah
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Yahya
Y
Elshimali
UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA; Department of Medicine, Division of General Internal Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA.
David
D
Elashoff
Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Edward B
EB
Garon
UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA; Department of Medicine, Division of Cancer Research and Training, Charles Drew University School of Medicine and Science, Los Angeles, CA.
Jaydutt
J
Vadgama
UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA; Department of Medicine, Division of Hematology-Oncology, UCLA David Geffen School of Medicine, Los Angeles, CA.
Richard
R
Pietras
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D047629:Estrogen Receptor beta / Q000187:drug effects*; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D013002:Somatomedins / Q000187:drug effects*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D000970:Antineoplastic Agents; D047629:Estrogen Receptor beta; D013002:Somatomedins