Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients.

Abstract

Simple SummaryGallbladder cancer is the sixth cause of death related to digestive tract tumors, with high mortality due to delayed diagnosis at advanced stages of the disease. Moreover, treatment options for advanced gallbladder cancer usually rely on cytotoxic chemotherapy, which is frequently ineffective. Since complete surgical removal at early stages represents the best chance for curative treatment, there is an urgent need for the discovery of effective biomarkers to assess individual risk and early detection of the disease. Equally important is the development of predictive markers for adequate selection of systemic therapies to improve patient prognosis, both in the adjuvant and palliative settings. In the following review, we summarize current and newly examined biomarkers and discuss their potential utility in the management of gallbladder cancer patients.Gallbladder cancer (GBC) is an aggressive disease that shows evident geographic variation and is characterized by a poor prognosis, mainly due to the late diagnosis and ineffective treatment. Genetic variants associated with GBC susceptibility, including polymorphisms within the toll-like receptors TLR2 and TLR4, the cytochrome P450 1A1 (CYP1A1), and the ATP-binding cassette (ABC) transporter ABCG8 genes, represent promising biomarkers for the stratification of patients at higher risk of GBC; thus, showing potential to prioritize cholecystectomy, particularly considering that early diagnosis is difficult due to the absence of specific signs and symptoms. Similarly, our better understanding of the gallbladder carcinogenic processes has led to identify several cellular and molecular events that may influence patient management, including HER2 aberrations, high tumor mutational burden, microsatellite instability, among others. Despite these reports on interesting and promising markers for risk assessment, diagnosis, and prognosis; there is an unmet need for reliable and validated biomarkers that can improve the management of GBC patients and support clinical decision-making. This review article examines the most potentially significant biomarkers of susceptibility, diagnosis, prognosis, and therapy selection for GBC patients, highlighting the need to find and validate existing and new molecular biomarkers to improve patient outcomes.