Precision medicine for urothelial bladder cancer: update on tumour genomics and immunotherapy

Abstract

Effective management of advanced urothelial bladder cancer is challenging. New discoveries that improve our understanding of molecular bladder cancer subtypes have revealed numerous potentially targetable genomic alterations and demonstrated the efficacy of treatments that harness the immune system. These findings have begun to change paradigms of bladder cancer therapy. For example, DNA repair pathway mutations in genes such as ERCC2, FANCC, ATM, RB1, and others can predict responses to neoadjuvant platinum-based chemotherapies and to targeted therapies on the basis of mutation status. Furthermore, an increasing number of pan-cancer clinical trials (commonly referred to as basket or umbrella trials) are enrolling patients on the basis of molecular and genetic predictors of response. These studies promise to provide improved insight into the true utility of personalized medicine in the treatment of bladder cancer and many other cancer types. Finally, therapies that modulate immune responses have shown great benefit in many cancer types. Several immune checkpoint inhibitors that target programmed cell death protein 1 (PD1), its ligand PDL1, and cytotoxic T lymphocyte-associated protein 4 (CTLA4) have already been approved for use in bladder cancer, representing the most important change to the urological oncologist's tool-kit in over a decade. These advances also provide opportunities for personalization of bladder cancer therapy.

An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle‐invasive bladder cancer (MIBC)

“…Immunotherapies are emerging treatment options for MIBC patients, but immunotherapeutic responses have been heterogeneous among MIBC patients . Moreover, immunotherapies are expensive for patients, so the accurate prediction of immunotherapeutic responses will be helpful to save medical costs for insensitive patients.…”

Identification of sex differences in tumor-specific T cell infiltration in bladder tumor-bearing mice treated with BCG immunotherapy

“…Bladder cancer is an exceedingly common disease comprised of diverse clinical and molecular subgroups that is approximately three times more prevalent in men than women (Felsenstein and Theodorescu, 2018). At initial diagnosis, ~75% of cancers are nonmuscle invasive with different grades, stages and risk levels (Sanli et al, 2017).…”

A húgyhólyag urothelialis daganatainak molekuláris alcsoportbeosztása és annak klinikai vonatkozásai

“…Ezen túl a ciszplatinterápia hatékonyságának előrejelzése az új checkpoint (ellen őr-zőpont)-gátló kezelések megjelenésével még inkább égető szükségűvé vált. A PDL-1-gátló és PD-1-gátló szerek a jelenlegi irányelvek szerint a másodvonalban ciszplatinrezisztens, valamint az első vonalban a ciszplatinkezelésre alkalmatlan betegeknek adhatók [5,7]. A ciszplatinkezelés hatékonyságának előrejelzése tehát utat nyithatna a checkpointgátlók haladéktalan alkalmazásának olyan esetekben, amelyekben a ciszplatinkezelés várhatóan nem lesz hatékony.…”