TY - JOUR
T1 - FGFR signaling and endocrine resistance in breast cancer
T2 - Challenges for the clinical development of FGFR inhibitors
AU - Servetto, Alberto
AU - Formisano, Luigi
AU - Arteaga, Carlos L.
N1 - Funding Information:
C.L.A receives or has received research grants from Pfizer, Lilly and Takeda; holds minor stock options in Provista; serves or has served in an advisory role to Novartis, Merck, Lilly, Daiichi Sankyo, Taiho Oncology, OrigiMed, Puma Biotechnology, Immunomedics, AstraZeneca, Arvinas and Sanofi; and reports scientific advisory board remuneration from the Susan G. Komen Foundation.
Funding Information:
UTSW Simmons Cancer Center P30 CA142543, CPRIT RR170061, NCI Breast SPORE P50 CA098131, Susan G. Komen Breast Cancer Foundation SAB1800010 grant, a Breast Cancer Research Foundation grant, and NCI R01CA224899.
Publisher Copyright:
© 2021
PY - 2021/12
Y1 - 2021/12
N2 - Fibroblast growth factors (FGFs) and their receptors (FGFRs) have been extensively investigated in solid malignancies, representing an attractive therapeutic target. In breast cancer, especially in estrogen receptor positive (ER+) subtype, FGFR signaling aberrations have been reported to contribute to proliferation, dedifferentiation, metastasis and drug resistance. However, clinical trials evaluating the use of FGFR inhibitors in breast cancer have had disappointing results. The different biological properties of distinct FGFR alterations and lack of established patient selection criteria, in addition to the early use of non-selective inhibitors, are possible reasons of this failure. Herein, we review the current knowledge regarding the role of FGFR signaling in endocrine resistance in breast cancer. We will also summarize the results from the clinical development of FGFR inhibitors in breast cancer, discussing future challenges to identify the correct cohorts of patients to enroll in trials testing FGFR inhibitors.
AB - Fibroblast growth factors (FGFs) and their receptors (FGFRs) have been extensively investigated in solid malignancies, representing an attractive therapeutic target. In breast cancer, especially in estrogen receptor positive (ER+) subtype, FGFR signaling aberrations have been reported to contribute to proliferation, dedifferentiation, metastasis and drug resistance. However, clinical trials evaluating the use of FGFR inhibitors in breast cancer have had disappointing results. The different biological properties of distinct FGFR alterations and lack of established patient selection criteria, in addition to the early use of non-selective inhibitors, are possible reasons of this failure. Herein, we review the current knowledge regarding the role of FGFR signaling in endocrine resistance in breast cancer. We will also summarize the results from the clinical development of FGFR inhibitors in breast cancer, discussing future challenges to identify the correct cohorts of patients to enroll in trials testing FGFR inhibitors.
KW - Breast cancer
KW - Endocrine resistance
KW - FGFR1
KW - Tyrosine kinase inhibitors
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U2 - 10.1016/j.bbcan.2021.188595
DO - 10.1016/j.bbcan.2021.188595
M3 - Review article
C2 - 34303787
AN - SCOPUS:85112777564
SN - 0304-419X
VL - 1876
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
IS - 2
M1 - 188595
ER -