TY - JOUR
T1 - Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype?
AU - Du, Fanny Le
AU - Eckhardt, Bedrich L.
AU - Lim, Bora
AU - Litton, Jennifer K.
AU - Moulder, Stacy
AU - Meric-Bernstam, Funda
AU - Gonzalez-Angulo, Ana M.
AU - Ueno, Naoto T.
PY - 2015
Y1 - 2015
N2 - Significant research has been conducted to better understand the extensive, heterogeneous molecular features of triple-negative breast cancer (TNBC). We reviewed published TNBC molecular classifications to identify major groupings that have potential for clinical trial development. With the ultimate aim to streamline translational medicine, we linked these categories of TNBC according to their geneexpression signatures, biological function, and clinical outcome. To this end, we define five potential clinically actionable groupings of TNBC: 1) basal-like TNBC with DNA-repair deficiency or growth factor pathways; 2) mesenchymal-like TNBC with epithelial-to-mesenchymal transition and cancer stem cell features; 3) immuneassociated TNBC; 4) luminal/apocrine TNBC with androgen-receptor overexpression; and 5) HER2-enriched TNBC. For each defined subtype, we highlight the major biological pathways and discuss potential targeted therapies in TNBC that might abrogate disease progression. However, many of these potential targets need clinical validation by clinical trials. We have yet to know how we can enrich the targets by molecular classifications.
AB - Significant research has been conducted to better understand the extensive, heterogeneous molecular features of triple-negative breast cancer (TNBC). We reviewed published TNBC molecular classifications to identify major groupings that have potential for clinical trial development. With the ultimate aim to streamline translational medicine, we linked these categories of TNBC according to their geneexpression signatures, biological function, and clinical outcome. To this end, we define five potential clinically actionable groupings of TNBC: 1) basal-like TNBC with DNA-repair deficiency or growth factor pathways; 2) mesenchymal-like TNBC with epithelial-to-mesenchymal transition and cancer stem cell features; 3) immuneassociated TNBC; 4) luminal/apocrine TNBC with androgen-receptor overexpression; and 5) HER2-enriched TNBC. For each defined subtype, we highlight the major biological pathways and discuss potential targeted therapies in TNBC that might abrogate disease progression. However, many of these potential targets need clinical validation by clinical trials. We have yet to know how we can enrich the targets by molecular classifications.
KW - Epithelial-mesenchymal transition
KW - Gene expression profiling
KW - Immunotherapy
KW - Targeted therapy
KW - Triple-negative breast cancer
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U2 - 10.18632/oncotarget.3849
DO - 10.18632/oncotarget.3849
M3 - Article
C2 - 25973541
AN - SCOPUS:84931094433
SN - 1949-2553
VL - 6
SP - 12890
EP - 12908
JO - Oncotarget
JF - Oncotarget
IS - 15
ER -