Biological Molecular Layer Classification of Muscle-Invasive Bladder Cancer Opens New Treatment Opportunities - Beyond the Abstract

The standard treatment for muscle-invasive bladder cancer is neoadjuvant chemotherapy following by surgery. However, some patients do not benefit from this scheme and they receive unnecessary treatment and toxicity. On the other hand, with the bloom of immunotherapies, it is necessary for the characterization of immune features of tumors. In this study, a “molecular layer classification” was established.

This classification identified, on the one hand, luminal and basal tumors and, on the other hand, immune-high and immune-low groups. It is noteworthy that these two classifications, defined by a non-supervised analysis, showed some overlapping (i.e, there are immune high basal and immune high luminal tumors), pointing out that the existence of an “immune subtype” with homogeneous molecular characteristics proposed previously in some clinical scenarios (such as bladder cancer, melanoma and triple-negative breast cancer), based on analysis where tumors are classified in excluding groups, should be carefully revised due to the implications these classifications could have in subsequent treatment of patients in the future.

Strikingly, this classification pointed out the existence of some possible therapeutic targets. For instance, luminal tumors had overexpression of androgen receptor and they may be treated with androgen receptor inhibitors. Basal tumors were more proliferative and they could be good responders to chemotherapy. Finally, the immune-positive high group had a high expression of PDL-1 and CTLA-4, both immunotherapy targets. In conclusion, in this work, a classification that may have therapeutic implications for the treatment of muscle-invasive bladder cancer was suggested.
BTA 2019 molecular layer classification

Proposed therapies based on the molecular layer classification.

Written by: Lucía Trilla-Fuertes, PhD, Biomedica Molecular Medicine SL, Angelo Gámez-Pozo, PhD, Molecular Oncology Lab, Hospital Universitario La Paz, Madrid, Spain, and Juan Ángel Fresno Vara, PhD Molecular Oncology & Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain, Biomedical Research Networking Center on Oncology-CIBERONC, ISCIII, Madrid, Spain

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