Raval Vishal, Parulekar Manoj, Singh Arun D
aThe Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Hyderabad, India.
bConsultant Ophthalmologist, Birmingham Children's Hospital, Birmingham, UK.
Ocul Oncol Pathol. 2022 Nov;8(3):149-155. doi: 10.1159/000524919. Epub 2022 May 9.
Over the last few decades, chemotherapy has become the main treatment of retinoblastoma, delivered through various routes: intravenous, intra-arterial, and intravitreal. Despite its efficacy, chemotherapy-related toxicity (ocular and systemic) and recurrences due to resistant tumor clones are common, highlighting the need for novel therapeutic agents. Recent advances in our understanding of the molecular drivers of Rb1 tumorigenesis and mechanisms of tumor resistance have afforded opportunities to explore novel targets such as the MDMX-p53 pathway (nutlin-3), histone deacetylase inhibitors, spleen tyrosine kinase inhibitors, and genetic and immune modulatory drugs. In this review, we discuss the limitations of current therapeutic strategies, candidate cellular pathways, current evidence for newer targeted drugs, and offer a look toward the future. Advances in the understanding of the molecular drivers of the RB pathway have provided opportunities to explore novel drugs with targeted effects, improved bioavailability, and reduced chemotoxicity.
在过去几十年中，化疗已成为视网膜母细胞瘤的主要治疗方法，通过多种途径给药：静脉内、动脉内和玻璃体内。尽管化疗有效，但化疗相关毒性（眼部和全身）以及耐药肿瘤克隆导致的复发很常见，这凸显了对新型治疗药物的需求。我们对Rb1肿瘤发生的分子驱动因素和肿瘤耐药机制的最新认识，为探索新型靶点提供了机会，如MDMX-p53通路（Nutlin-3）、组蛋白去乙酰化酶抑制剂、脾酪氨酸激酶抑制剂以及基因和免疫调节药物。在本综述中，我们讨论了当前治疗策略的局限性、候选细胞通路、新型靶向药物的现有证据，并展望了未来。对RB通路分子驱动因素认识的进展为探索具有靶向作用、提高生物利用度和降低化学毒性的新型药物提供了机会。
