Details

Autor(en) / Beteiligte

• Mishra, Shravan Kumar
• Kumari, Niraj
• Krishnani, Narendra

Titel

Molecular pathogenesis of gallbladder cancer: An update

Ist Teil von

• Mutation research, 2019-11, Vol.816-818, p.111674-111674, Article 111674

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• •Mutations in oncogenes occur more frequently in GBC patients and are more common at advance stage of disease.•The mutation frequency of codon 12 and 13 of KRAS gene is lower in GBC patients of North and South America (0–11%) compared to GBC patients in Asia (2.0–41.0%).•The modulation of immune check point is emerging as a promising immunotherapeutic approach to treat GBC. Up-regulated expression of PD-L1 in ERBB2/3 mutant GBC cells leads to the inhibition of normal T-cell mediated cytotoxicity in-vitro through the activation of PI3K/AKT signaling pathway. ERBB2 and ERBB3 mutations have been reported in 16% and 12% cases of GBC respectively and their association with PDL1 expression may open a new area of targeted therapy in these patients. Gallbladder carcinoma (GBC) is the most aggressive gastrointestinal malignancy throughout the world, with wide geographical variance. It is the subtype of biliary tract malignancy that has the poorest prognosis and lower survival among all biliary tract malignancies. Various factors are associated with GBC pathogenesis such as environmental, microbial, metabolic and molecular. Chronic inflammation of gallbladder due to presence of gallstone or microbial infection (eg. Salmonella or H. pylori) results in sustained production of inflammatory mediators in the tissue microenvironment, which can cause genomic changes linked to carcinogenesis. Genetic alterations are one of the major factors, associated with aggressiveness and prognosis. Researches have been done to explore suitable biomarker for early diagnosis and identify altered molecular pathways to develop appropriate biomarkers for early diagnosis, therapy and predicting prognosis. Different agents for targeted therapy against actionable mutations of molecules like EGFR, VEGF, mTOR, HER2, PDL-1, PD-1, MET, PI3K, N-cadherin, VEGFR, MEK1 and MEK2 are being tried. Despite these advancements, there is dismal improvement in the survival of GBC patients. Genetic aberrations other than actionable mutations and epigenetic modification including aberrant expressions of micro-RNAs, are also being studied both as diagnostic biomarker and therapeutic targets. Complex pathogenesis of GBC still needs to be unfolded. In this review we focus on the molecular pathogenesis of GBC elucidated till date along with future directions that can be explored to achieve better management of GBC patients.