How obesity worsens outcomes in pancreatic ductal adenoocarcinoma (PDAC) is not clear. Incio et al. showed that obesity promoted desmoplasia, increased tumour growth and impaired delivery of chemotherapy in mouse models of PDAC; these phenotypes were reversed by inhibition of angiotensin II receptor type 1 (AT1). Desmoplasia was promoted by crosstalk between pancreatic stellate cells, neutrophils and adipocytes, and loss of this network prevented tumour growth. Obese patients with PDAC also had increased desmoplasia and reduced chemotherapy response, indicating the therapeutic relevance of this pathway.
References
Incio, J. et al. Obesity-induced inflammation and desmoplasia promote pancreatic cancer progression and resistance to chemotherapy. Cancer Discov. https://dx.doi.org/10.1158/2159-8290.CD-15-1177 (2016)
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Seton-Rogers, S. Connecting obesity and cancer mechanistically. Nat Rev Cancer 16, 411 (2016). https://doi.org/10.1038/nrc.2016.69
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DOI: https://doi.org/10.1038/nrc.2016.69