Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Abstract

In the last years, we have witnessed remarkable advances in targeted therapies for cancer patients. There is a growing effort to either replace or reduce the dose of unspecific, systemic (chemo)therapies, given the associated short- and long-term side effects, by introducing more specific targeted therapies as single or combination agents. Due to the well-known implications of the immune system and epigenetic landscape in modulating cancer development, both have been explored as potential targets in several malignancies, including those affecting the genitourinary tract. As the immune system function is also epigenetically regulated, there is rationale for combining both strategies. However, this is still rather underexplored, namely in urological tumors. We aim to briefly review the use of immune therapies in prostate, kidney, bladder, and testicular cancer, and further describe studies providing supporting evidence on their combination with epigenetic-based therapies.

Practicability of clinical application of bladder cancer molecular classification and additional value of epithelial-to-mesenchymal transition: prognostic value of vimentin expression

“…This subtype has dismal prognosis and survival has remained overall unchanged in the last couple of decades. Recently, immunotherapy has proved useful in the metastatic setting, with several agents being approved and shown to be effective [39,40]. However, again, there is a need for better biomarkers predictive of response to specific agents [41,42], that can be determined in tissue samples upon radical cystectomy and also non-invasively, in liquid biopsy context.…”

Targeting Germ Cell Tumors with the Newly Synthesized Flavanone-Derived Compound MLo1302 Efficiently Reduces Tumor Cell Viability and Induces Apoptosis and Cell Cycle Arrest

“…Moreover, MLo1302 may be explored in combinatory strategies, either with cisplatin or other targeted therapies, to improve treatment of TGCT patients. Specifically, following one line of investigation of our group and our previous results [ 15 , 58 ], we intend to combine MLo1302 both with histone deacetylase inhibitors (HDACis) Belinostat and Panobinostat (to assess synergy with hypomethylating properties of MLo1302) and also with anti-PD1/PDL1 agents (to assess the potential for epigenetic activation of tumor microenvironment and enhance response to immunotherapies). Finally, the expression array advances many molecular pathways by which MLo1302 induces cell death (besides downregulation of NOL3 and increase caspase 8 and 2 activation) and these may be explored in future studies.…”

Tackling tumor microenvironment through epigenetic tools to improve cancer immunotherapy

“…For NMIBC, treatment mostly consists of TURBT eventually complemented with mitomycin or Bacillus Calmette-Guérin (BCG) instillation, whereas radical cystectomy with lymphadenectomy remains the gold standard for MIBC, complemented with neo-adjuvant or adjuvant cisplatin-based chemotherapy, which is also the main option for metastatic BC [ 209 ]. Recently, immunotherapies targeting PD-1/PD-L1 immune checkpoint were approved for BC patients that are refractory or ineligible to cisplatin-based chemotherapy [ 210 ]. Although chemotherapy and immunotherapy have improved the outcome of locally advanced and metastatic disease, 5-year survival remains poor (36% and 5%, respectively) [ 207 ].…”