Editors' ChoiceCancer

Bosom Buddies: Close Connections Between Breast and Bladder Cancer

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Science Translational Medicine  26 Feb 2014:
Vol. 6, Issue 225, pp. 225ec36
DOI: 10.1126/scitranslmed.3008709

Just as the name implies, high-grade muscle-invasive bladder cancer (MIBC) is extremely aggressive. The standard of care is radical surgery and cisplatin-based chemotherapy, but this approach is effective in only 30 to 40% of patients. To improve patient outcomes, it will be important to prospectively identify which patients will respond to therapy and to identify new treatment options for those who will not. Some cancers, including breast cancer, have distinct molecular subtypes, each of which responds differently to therapies. Choi and colleagues set out to elucidate whether MIBC also has distinct molecular subtypes that can inform treatment decisions.

Using whole-genome gene expression profiling of 73 primary bladder cancers, the authors identified three major subtypes of MIBC, named according to their gene expression signatures (luminal, basal, and p53-like luminal). Surprisingly, at the molecular level, these subtypes closely resembled breast cancer subtypes. Luminal MIBC showed activation of the potentially druggable peroxisome proliferator activated receptor γ (PPARγ), estrogen receptor (ER), and fibroblast growth factor receptor 3 (FGFR3) signaling pathways. Basal MIBC was characterized by squamous differentiation, p63 expression, and activation of the targetable epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), and nuclear factor κB (NF-κB) pathways. Patients with basal-like tumors had the poorest outcome, but among these, patients with tumors showing evidence of immune infiltration had a better response to chemotherapy. Last, the p53-like luminal subtype of bladder cancer was resistant to neoadjuvant chemotherapy, similar to p53 wild-type breast cancers. Using a similar approach, an independent group led by Damrauer and colleagues also identified subtypes of bladder cancer, recognizing their close relation to breast cancer.

Together, these findings support the notion that we have a lot to learn from cross-tissue comparisons in cancer. Discoveries in one tumor type contribute to the understanding and treatment of another. In fact, cancers originating from different tissues can be more closely related at a molecular level than tumors from the same tissue. Maybe the old adage is true for cancer—if you want to know a cancer, get to know its friends.

W. Choi et al., Identification of distinct Basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25, 152–165 (2014). [PubMed]

J. S. Damrauer et al., Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc. Natl. Acad. Sci. U.S.A., published online 10 February 2014 (10.1073/pnas.1318376111). [Abstract]

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