Novel Target therapy in the gastrointestinal cancers

Gastrointestinal cancers are of different types mainly focusing on the biliary tract cancers (BTC) are a heterogeneous group of cancers that are clinically and genetically divergent. BTC can be divided anatomically into gallbladder cancers (GBC), intrahepatic cholangiocarcinomas (IHCC), hilar cholangiocarcinomas (HCC), and extrahepatic cholangiocarcinomas (EHCC).

Personalized cancer medicines have occurred in current years and a number of targeted drugs have emerged. Various targeted therapies like erlotinib, trastuzumab and cetuximab have been approved in lung, breast, and colon cancers respectively.Combination chemotherapy involving cisplatin and gemcitabine is the current standard of care in the metastatic setting.

BTC are rare malignancies with poor prognosis with GBC being the most common among all BTC. Risk factors for BTC include parasitic infections by liver flukes, gallstones, diabetes mellitus, obesity, alcohol, inflammatory bowel disease, bile duct cysts, smoking, and hepatitis B and C. The presence of gallstones is by far the most important risk factor. The exact mechanism by which gallstones cause carcinogenesis is unknown but is probably due to persistent inflammation leading to dysplasia and accumulation of loss of heterozygosity at various tumour suppressor genes.

GBC have the worst prognosis among all BTC. Treatment of early BTC is surgery which offers potential cure. For advanced inoperable BTC systemic therapy is the only option. Poor prognostic factors after resection include the presence of lymph node metastases, positive margins, and poor differentiation. The use of chemotherapy over best supportive care was first supported in a clinical trial comparing combination of 5-fluorouracil and etoposide vs. best supportive care.

Recent studies revealed multiple clinically targetable mutations in BTC. Different molecular pathways are incriminating in carcinogenesis, and agents targeting these pathways have shown some efficacy in BTC cell lines.

GBC, the most aggressive cancer among all, is categorized as an orphan disease. Despite recent advances in our knowledge on the pathogenesis of BTC at the molecular level prognosis remains poor.

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