Dataset Information

Current biologics for treatment of biliary tract cancers.

ABSTRACT: Biliary tract cancers (BTC) is a group of malignancies that arise from the epithelial cells of the biliary tree. These cancers are typically classified by anatomic site of origin: intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC). To date, complete surgical resection remains the mainstay of treatment especially for earlier stage disease. Unfortunately, most patients present with advanced or metastatic disease, when systemic chemotherapy is the only treatment option. Due to the paucity of effective treatments, BTCs have a dismal prognosis. There is a tremendous need to better understand the disease biology, discover new therapies, and improve clinical outcomes for this challenging disease. Next-generation sequencing has produced a more accurate and detailed picture of the molecular signatures in BTCs. The three BTC histologic subtypes are, in fact, quite molecularly distinct. IHCC commonly contain FGFR2 fusions and IDH 1 and 2 mutations, whereas EHCC and GBC tend to carry mutations in EGFR, HER2, and MAPK pathway. In light of this emerging knowledge, clinical trials have become more biomarker-driven, which allows capturing of subsets of patients that are most likely to respond to certain therapies. Many new and promising targeted therapeutics are currently in the pipeline. Here we review the genetic landscape of BTCs while focusing on new molecular targets and targeted therapeutics currently being investigated in biomarker-driven clinical trials.

SUBMITTER: Zhao DY

PROVIDER: S-EPMC5506280 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Current biologics for treatment of biliary tract cancers.

Zhao Diana Y DY Lim Kian-Huat KH

Journal of gastrointestinal oncology 20170601 3

Biliary tract cancers (BTC) is a group of malignancies that arise from the epithelial cells of the biliary tree. These cancers are typically classified by anatomic site of origin: intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC). To date, complete surgical resection remains the mainstay of treatment especially for earlier stage disease. Unfortunately, most patients present with advanced or metastatic disease, when systemic chemothera ...[more]

PMID: 28736630

Similar Datasets

Project description:Biliary tract cancers (BTCs), comprising intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder adenocarcinoma, continue to be challenging to manage. Conventional chemotherapy regimens for advanced disease are limited in both options and benefits, and more effective perioperative regimens are also needed. Over the last decade, immunotherapy has had a profound impact on the management of many solid tumor types, particularly in using immune checkpoint inhibition to enable a tumor-directed T cell response. Immunotherapy administered on its own has had limited utility in BTCs, in part due to a hostile immune microenvironment and the relative infrequency of biomarker-based tumor-agnostic indications for immunotherapy. However, immunotherapy in conjunction with chemotherapy, molecularly targeted therapies, and/or anti-angiogenic therapies has gained traction, supported by evidence that these agents can impart favorable immunomodulatory effects on the tumor microenvironment. The TOPAZ-1 trial led to the first BTC-specific immunotherapy approval, establishing the combination of durvalumab with gemcitabine and cisplatin as the preferred first-line treatment for advanced or metastatic disease. Recently, the KEYNOTE-966 trial showed positive results for the combination of pembrolizumab with gemcitabine and cisplatin in the same setting, adding further evidence for the addition of immune checkpoint inhibition to the standard chemotherapy backbone. Meanwhile, advances in the molecular profiling of BTCs has contributed to the recent proliferation of molecularly targeted therapeutics for the subset of BTCs harboring alterations in IDH1, FGFR2, MAP kinase signaling, HER2, and beyond, and there has been great interest in investigating combinations of these agents with immunotherapy. Emerging immunotherapy strategies beyond immune checkpoint inhibition are also being studied in BTCs, and these include immunostimulatory receptor agonists, Wnt signaling modulators, adoptive cell therapy, and cancer vaccines. A large number of trials are underway to explore promising new combinations and immune-targeted strategies, offering opportunities to expand the role of immunotherapy in BTC management in the near future.

Project description:Background & aimsGallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.MethodsWe pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.ResultsDuring 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.ConclusionWe observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.Lay summaryOur findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

Dataset Information

Current biologics for treatment of biliary tract cancers.

Publications

Current biologics for treatment of biliary tract cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets