Translational screening platform to evaluate chemotherapy in combination with focal therapy for retinoblastoma.

Retinoblastoma is the most common pediatric eye cancer. It is currently treated with a limited number of drugs, adapted from other pediatric cancer treatments. Drug toxicity and relapse of the disease warrant new therapeutic strategies for these young patients. In this study, we developed a robust tumoroid-based platform to test chemotherapeutic agents in combination with focal therapy (thermotherapy) - a treatment option widely used in clinical practice - in accordance with clinically relevant trial protocols. The model consists of matrix-embedded tumoroids that retain retinoblastoma features and respond to repeated chemotherapeutic drug exposure similarly to advanced clinical cases. Moreover, the screening platform includes a diode laser (810 nm, 0.3 W) to selectively heat the tumoroids, combined with an on-line system to monitor the intratumoral and surrounding temperatures. This allows the reproduction of the clinical settings of thermotherapy and combined chemothermotherapy treatments. When testing the two main drugs currently used in clinics to treat retinoblastoma in our model, we observed results similar to those clinically obtained, validating the utility of the model. This screening platform is the first system to accurately reproduce clinically relevant treatment methods and should lead to the identification of more efficient drugs to treat retinoblastoma.

Natural and synthetic retinoids in preclinical colorectal cancer models.

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. Although targeted therapy in combination with chemotherapy in CRC prolongs the overall survival of patients with metastatic disease, acquired resistance and relapse hinder their clinical benefits. Moreover, patients with some specific genetic profile are unlikely to benefit from targeted therapy, suggesting the need for safe and effective treatment strategies. Retinoids, comprising of natural and synthetic analogs, are a class of chemical compounds that regulate cellular proliferation, differentiation, and cell death. Retinoids have been used in the clinic for several leukemias and solid tumors, either as single agents or in combination therapy. Furthermore, retinoids have shown potent chemotherapeutic and chemopreventive properties in different cancer models, including CRC. In this review, we summarize the major preclinical findings in CRC in which natural and synthetic retinoids showed promising antitumor activities and stress on the proposed mechanisms of action. Understanding of the retinoids' antitumor mechanisms would provide insights to support and warrant their development in the management of CRC.