TY - JOUR
T1 - Progress in small molecule therapeutics for the treatment of retinoblastoma
AU - Pritchard, Eleanor M.
AU - Pritchard, Eleanor M.
AU - Dyer, Michael A.
AU - Dyer, Michael A.
AU - Dyer, Michael A.
AU - Guy, R. Kiplin
N1 - Publisher Copyright:
© 2016 Bentham Science Publishers.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors.
AB - While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors.
KW - Chemoreduction
KW - Ocular drug delivery
KW - Retinoblastoma
UR - http://www.scopus.com/inward/record.url?scp=84961584035&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84961584035&partnerID=8YFLogxK
U2 - 10.2174/1389557515666150722100610
DO - 10.2174/1389557515666150722100610
M3 - Article
C2 - 26202204
AN - SCOPUS:84961584035
SN - 1389-5575
VL - 16
SP - 430
EP - 454
JO - Mini-Reviews in Medicinal Chemistry
JF - Mini-Reviews in Medicinal Chemistry
IS - 6
ER -