Review of Experimental Studies to Improve Radiotherapy Response in Bladder Cancer: Comments and Perspectives

Abstract

Bladder cancer is among the top ten most common cancer types in the world. Around 25% of all cases are muscle-invasive bladder cancer, for which the gold standard treatment in the absence of metastasis is the cystectomy. In recent years, trimodality treatment associating maximal transurethral resection and radiotherapy combined with concurrent chemotherapy is increasingly used as an organ-preserving alternative. However, the use of this treatment is still limited by the lack of biomarkers predicting tumour response and by a lack of targeted radiosensitising drugs that can improve the therapeutic index, especially by limiting side effects such as bladder fibrosis. In order to improve the bladder-preserving treatment, experimental studies addressing these main issues ought to be considered (both in vitro and in vivo studies). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, we conducted a literature search in PubMed on experimental studies investigating how to improve bladder cancer radiotherapy with different radiosensitising agents using a comprehensive search string. We made comments on experimental model selection, experimental design and results, formulating the gaps of knowledge still existing: such as the lack of reliable predictive biomarkers of tumour response to chemoradiation according to the molecular tumour subtype and lack of efficient radiosensitising agents specifically targeting bladder tumour cells. We provided guidance to improve forthcoming studies, such as taking into account molecular characteristics of the preclinical models and highlighted the value of using patient-derived xenografts as well as syngeneic models. Finally, this review could be a useful tool to set up new radiation-based combined treatments with an improved therapeutic index that is needed for bladder preservation.

Urological Cancer Panorama in the Second Year of the COVID-19 Pandemic

“…Silina et al [20] reviews bladder sparing strategies with the use of radiotherapy and chemotherapy combined, a very interesting therapeutic approach for invasive bladder cancer, that is emerging also as a therapeutic possibility in the context of medical system collapse for scheduled surgeries suffered by the COVID-19 health crisis. Based on the issue that strategies to radio-sensitize tumors and spare normal bladder tissue to improve treatment safety, a systematic search and literature review is performed.…”

EZH2 targeting to improve the sensitivity of acquired radio-resistance bladder cancer cells

“…Therefore, bladder-preserving based radiotherapy is recommended as an alternative to surgery for the treatment of BCa. Moreover, radiation therapy is also suitable for BCa patients who have recurred after surgery [4] . In clinic, fractionated irradiation(FI) is commonly adopted to avoid and reduce the damage effect of radiation on normal tissues.…”

Tyro3 Targeting as a Radiosensitizing Strategy in Bladder Cancer through Cell Cycle Dysregulation

“…Selectively increasing bladder tumor sensitivity to radiation could improve the efficacy of this treatment, limiting its side effects and reducing the need for cystectomy. However, there is a limited number of experimental studies investigating radiosensitization strategies of bladder tumors, which highlights the urgent need to perform additional studies and optimize this approach [ 9 ].…”