DECODING GALLBLADDER CARCINOMA: AN OVERVIEW OF ITS TRENDS, MECHANISMS, AND GENETIC UNDERPINNINGS

ABSTRACT

Gallbladder cancer (GBC) is a rare but highly aggressive malignancy with a poor prognosis, especially in advanced stages. The disease is frequently diagnosed at advanced stages due to its asymptomatic nature in early progression, resulting in poor prognosis and limited treatment options. This review offers a thorough examination of the current state of GBC, focusing on its diagnosis, treatment, and emerging research directions. Using a systematic literature search, we identified key studies related to GBC’s diagnostic challenges, treatment modalities, and innovative therapeutic approaches. Our findings highlight the key points associated with  achieving early and precise diagnosis of GBC, thus leading to potentially curative surgical interventions. Molecular insights demonstrate frequent mutations in TP53, KRAS, PIK3CA, BRAF, and EGFR, along with promoter hypermethylation of tumor suppressor genes (APC, CDKN2A, ESR1) and deregulation of miRNAs (miR-155, miR-29c-5p, miR-133a-3p) and lncRNAs (H19, LINC00152, CRNDE). Dysregulated signalling pathways, including PI3K/AKT, MAPK, and TGF-β/SMAD, contribute to tumor proliferation, invasion, and chemoresistance. Current treatment options are largely limited to gemcitabine-based chemotherapy regimens, such as Gem Cis, which, despite their use, come with notable limitations and adverse effects. Nevertheless, the review points to promising future developments, must prioritize large-scale, collaborative research, clinical validation of biomarkers, and equitable access to advanced therapies, including the need of diagnostic tools for early detection, improved chemotherapy protocols, targeted therapies informed by molecular insights into GBC, and the exploration of immunotherapy. Addressing these challenges and leveraging emerging therapeutic strategies could substantially enhance patient outcomes in GBC.

Keywords – Gallbladder cancer (GBC), epidemiology, pathogenesis, gene mutation and alteration, tumour suppressor.