TY - JOUR
T1 - HDAC inhibitors for the treatment of cutaneous T-cell lymphomas
AU - Rangwala, Sophia
AU - Zhang, Chunlei
AU - Duvic, Madeleine
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/3
Y1 - 2012/3
N2 - Epigenetic modification by small-molecule histone deacetylase inhibitors (HDAC-Is) has been a promising new antineoplastic approach for various solid and hematological malignancies, particularly for cutaneous T-cell lymphoma (CTCL). Vorinostat, a pan-HDAC-I and, most recently, romidepsin, a bicyclic pan-HDAC-I, have been US FDA approved for treatment of relapsed or refractory CTCL. However, because many patients do not reach the 50% partial response mark and response is not always sustainable, overcoming HDAC-I resistance by adding other agents or finding more selective molecules is an important clinical problem in realizing the full clinical potential of HDAC-Is. In this review, we discuss the molecular basis for HDAC-I function in cancer, the clinical response and side-effect profile experienced by CTCL patients, and the progress made in attempting to identify biomarkers of response and resistance, as well as synergistic combination therapies.
AB - Epigenetic modification by small-molecule histone deacetylase inhibitors (HDAC-Is) has been a promising new antineoplastic approach for various solid and hematological malignancies, particularly for cutaneous T-cell lymphoma (CTCL). Vorinostat, a pan-HDAC-I and, most recently, romidepsin, a bicyclic pan-HDAC-I, have been US FDA approved for treatment of relapsed or refractory CTCL. However, because many patients do not reach the 50% partial response mark and response is not always sustainable, overcoming HDAC-I resistance by adding other agents or finding more selective molecules is an important clinical problem in realizing the full clinical potential of HDAC-Is. In this review, we discuss the molecular basis for HDAC-I function in cancer, the clinical response and side-effect profile experienced by CTCL patients, and the progress made in attempting to identify biomarkers of response and resistance, as well as synergistic combination therapies.
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U2 - 10.4155/fmc.12.6
DO - 10.4155/fmc.12.6
M3 - Review article
C2 - 22416775
AN - SCOPUS:84863367140
SN - 1756-8919
VL - 4
SP - 471
EP - 486
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
IS - 4
ER -