New Hopes in Retinoblastoma Treatment

Abstract

Survival rates of retinoblastoma have increased dramatically during the last decade. The current major treatment modalities for retinoblastoma include enucleation, intravenous chemoreduction, external beam therapy, focal treatments (such as brachytherapy and transpupillary thermotherapy), subconjunctival chemotherapy and selective ophthalmic artery chemotherapy. Although current treatment modalities have improved survival rates as well as eye salvage, new treatment modalities are expected to arise in the near future, since above mentioned non-targeted treatments have extensive side effects. Recent advances in genetic analysis of retinoblastoma 1 (RB1) mutations and pathways leading to retinoblastoma may provide vital information for the development of new targeted therapies which are less toxic. Keywords: Genetics, Retinoblastoma, RB1 mutation, Targeted treatments ÖZET Retinoblastom Tedavisinde Yeni UmutlarSon on yılda retinoblastomda sağ kalım oranları dramatik olarak artmıştır. Enükleasyon, intravenöz kemoredüksiyon, dışsal ışın radyoterapi, fokal tedaviler (brakiterapi ve transpupiller termoterapi gibi), subkonjonktival kemoterapi, selektif oftalmik arter kemoterapi retinoblastomda kullanılan önemli tedavi modaliteleridir. Yeni tedavi seçenekleri göz küresinin kurtarılması ve sağkalım oranlarında iyileşme sağlamasına rağmen, özgül olmayan kemoterapi ajanlarının yaygın yan etkileri nedeniyle gelecekte yeni tedavi modalitelerine ihtiyaç duyulmaktadır. Retinablastom 1RB1 mutasyonlarının gen analizi ve retinoblastom oluşumunu sağlayan yolaklardaki son gelişmeler; daha az toksisitesi olan hedeflenmiş terapilerin gelişiminde önemli bilgiler sağlayacaktır.

The Role of Intraarterial Chemotherapy in the Management of Retinoblastoma

“…It is crucial to emphasize the role of animal models in exploring retinoblastoma tumorigenesis and testing new therapies. New treatment modalities for retinoblastoma include angiogenic inhibitors and various targeted therapies (see Figure 8) [42][43][44].…”

“…Murine retinoblastoma models were used to study these vascular-targeting agents. It was found that they induce apoptosis and cause minimal necrosis [43]. Following subconjunctival administration, both agents have a maximal effect on tumour vasculature at day 1 [42].…”

“…Tumour-associated macrophages (TAMs) and matrix metalloproteinases (MMPs) play an important role in tumorigenesis [43]. MMPs are responsible for the degradation of the extracellular matrix and take part in angiogenesis, cell proliferation, and metastasis [43]. TAMs were found to increase the levels of MMPs [43].…”

“…MMPs are responsible for the degradation of the extracellular matrix and take part in angiogenesis, cell proliferation, and metastasis [43]. TAMs were found to increase the levels of MMPs [43]. erefore, both TAMs and MMPs are potential therapeutic targets.…”

“…Studies on murine retinoblastoma models have proven that anecortave acetate reduces the expression of matrix metalloproteinases and as a consequence inhibits tumour growth [42]. On the other hand, TAMs are targeted by liposomal clodronate which causes their depletion and in fact improves tumour control [43].…”