Treatment of Patients with Bile Duct Cancer Could be Enhanced with Tailored Medications that Target Key Protein

Bile duct cancer treatments could be improved by tailored medications that target the levels of a key protein in patients, according to the findings of a new published in Cancer Research.

Researchers in the UK and Thailand uncovered that protein PRH/HHEX is a key driver of Cholangiocarcinoma (CCA), and increased levels affect the cancer’s response to therapy.

Dr. Padma Sheela Jayaraman, from the Institute of Cancer and Genomic Sciences at the University of Birmingham, said in a press release that, “Clinical efficacy of chemotherapeutic strategies is likely to depend on PRH expression level. Tailoring patient medication according to the individual level of PRH expression could improve clinical usefulness of several compounds, recently suggested as potential novel treatments for bile duct cancer.”

The researchers noted that Aberrant Notch and Wnt signalling are known drivers of CCA, however, the underlying factors controlling these pathways were not previously known. Their analysis found that the hyper-activation of these drivers is linked to the dysregulation of PRH. Based on their findings, they suggest new therapeutic options based on the dependence of specific Wnt, Notch, and CDK4/6 inhibitors on PRH activity.

They demonstrate that expression of PPH is elevated in cases of CCA and that reduction in PRH levels reduced CCA tumour growth in a model of cancer. Their results showed that high PRH expression in primary human biliary epithelial cells isolated from human liver, by Dr Simon Afford from the University of Birmingham’s Centre for Liver and Gastrointestinal Research, tended to increase cancer cell properties such as invasion and anchorage-independent growth.

Professor Kevin Gaston, from the University of Nottingham School of Medicine and Biodiscovery Institute, stated of the findings: “We are excited by the outcomes of this international collaborative study and we are working towards translating these findings into new ways of treating individual patients in the UK and in Thailand, where there is a particularly high incidence of CCA.”