Targeted Therapy in Retinoblastoma:Promise and Progress

Retinoblastoma is a malignant tumor that arises from immatureretinal cells. It is the most common primary intraocularmalignancy in children. Retinoblastoma develops due to themutations that inactivate both copies of the retinoblastoma(RB) tumor suppressor gene, leading to uncontrolled cellgrowth. Traditionally, retinoblastoma has been treated withtherapies such as chemotherapy, radiation therapy, cryotherapy,and laser therapy. However, these conventional treatmentscan have significant side effects including loss of vision andsecondary cancers. Despite the advancement in the treatmentstrategies, retinoblastoma remains a significant challenge dueto its aggressive nature and potential for metastasis. Targetedtherapy has emerged as a promising approach for the treatmentof retinoblastoma with fewer side effects. It works bytargeting specific molecular pathways that are dysregulatedin cancer cells, so it is able to more selectively disrupt cancergrowth while sparing normal cells. For example, one ofthe most promising targeted therapies for retinoblastoma isthe use of small molecule inhibitors that target the mitogenactivatedprotein kinase (MAPK) pathway. This pathway isoften activated in retinoblastoma cells, and its activation is associatedwith increased cell proliferation and survival. In addition,the inhibitors of the other dysregulated pathways in retinoblastomalike PI۳K/AKT/mTOR and EGFR show potentialfor high-risk or relapsed/refractory diseases. There are alsothe therapeutic antagonists of some molecules overexpressedin this disease, like inhibitors of MDM۲ in p۵۳ pathway andhistone deacetylase inhibitors. One may refer to SJ۱۷۲۵۵۰ andBIRO۱ as examples for these inhibitors, respectively. CircularRNAs (circRNAs) are another type of newly discoveredpotential therapeutic targets which serve as the regulators ofRB progression. Resistance to targeted therapy often limitslong-term success. Research efforts aim to develop combinatorialapproaches to overcome resistance, but more progressis required before this can impact clinical practice. Continuedprogress in this area may transform retinoblastoma into a fullycurable cancer.

کلیدواژه ها:

Retinoblastoma ، Targeted therapy ، Signaling pathway ، Modern approaches ، Cancer genetics