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Gallbladder Cancer: Epigenetic Landscape, Targeted Therapy, and Prospect of Epitherapy

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Gallbladder Cancer

Abstract

Gallbladder carcinoma (GBC) is among the most malignant neoplasms of the biliary tract with poor prognosis and reduced survival rates in different geographic locations of the world. Various risk factors, including gall stone, obesity, dietary habit, bacterial (e.g., H. pylori) infection, etc., are proposed but we are still unaware of a definite or specific causative factor. Most patients present for treatment with an advanced and inoperable state where the effect of conventional therapy becomes limiting or ineffective. Studies on the molecular pathology of GBC indicated numerous known genetic and epigenetic impairments responsible, but the exact mechanism of gallbladder cancer is yet to be revealed. With the advent of latest technology, investigations are continued to identify suitable biomarkers appropriate for early diagnosis and prognosis of GBC. This review provides an overview of the epigenetic mechanisms associated with gallbladder carcinoma, such as DNA methylation, histone modifications, and the role of non-coding RNAs. The non-coding RNAs (e.g., microRNAs, long non-coding RNAs, and circular RNAs) play significant role, directly or indirectly, in the transcriptional regulation of cancer associated target genes. It also includes brief description of the implications of promising epigenetic biomarkers (both coding and non-coding), identified in tissue samples or in circulating body fluids, in early detection, diagnosis and or prognosis of gallbladder cancer. The review has particularly discussed the concept of epigenetically targeted therapy, emphasizing the prospects of targeting some of the commonly identified cancer biomarkers, currently under preclinical or clinical investigations in other cancers, in the treatment of gallbladder cancer.

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Acknowledgment

We gratefully acknowledge SERB-DST and ICMR, Govt. of India, New Delhi, for providing financial support to PKT and fellowship to NS (DST) and AT (ICMR) for conducting the works quoted in this review.

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Sharma, N., Tomar, A., Tiwari, P.K. (2023). Gallbladder Cancer: Epigenetic Landscape, Targeted Therapy, and Prospect of Epitherapy. In: Kumar Shukla, V., Pandey, M., Dixit, R. (eds) Gallbladder Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-19-6442-8_12

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