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    Bladder Ca subtypes ID’d, may yield personalized therapies

     

    Now, with additional tumor samples and genomic data, the TCGA investigators were able to take the well-known luminal and basal subtypes of bladder cancer and further stratify them into five distinct subtypes: luminal, luminal-papillary, luminal-infiltrated, basal/squamous, and the new “neuronal” category, which was identified in 5% of samples and is characterized by “expression of both neuroendocrine and neuronal genes, as well as a high cell-cycle signature reflective of a proliferative state,” according to the investigators.

    Why the neuronal subtype with its higher mutational rate would be associated with a favorable prognosis needs to be researched further, Dr. Lerner said in an interview with Urology Times.

    “It may just be that there's better recognition by the immune system, but there could be other factors at work,” said Dr. Lerner, senior author of the report in Cell.

    Also see: Better models needed for predicting bladder Ca recurrence

    The TCGA investigators have encouraged others to take their data and use it to develop prospective clinical trials to see if targeting the subtypes does indeed result in improved clinical outcomes.

    Some compelling results have already emerged based on the previously published TCGA classification. One notable example is a phase II study reported in The Lancet (2016; 387; 1909-20) showing that patients with metastatic or unresectable bladder cancers of the luminal-infiltrated subtype tend to respond well to treatment with the immuno-oncologic agent atezolizumab (Tecentriq), a PD-L1 inhibitor.

    “We certainly think that it's incumbent upon pharma to really look at these types of predictive biomarkers in their clinical trials,” Dr. Lerner told Urology Times. “It makes a lot of sense for immuno-oncology agents, but it also makes sense for targeted therapies, because there are specific pathways of targets that are activated in these different subtypes.”

    More from Urology Times:

    Bladder Ca photothermal treatment yields encouraging results

    Smoking linked to tumor heterogeneity for bladder Ca

    Genomic research may explain resistance to immunotherapy


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    Andrew Bowser
    Andrew Bowser is a medical writer based in Brooklyn, New York.

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