The prognosis of patients with biliary tract cancers is poor and most patients are diagnosed with advanced stages where treatment intent’s is typically palliative. In those patients, subsequent therapeutic options after progression on first line chemotherapy are limited. In recent years, the landscape of treatment of bile duct cancers has witnessed several changes and several novel treatment targets have been identified. Molecular profiling is now recommended and represents an opportunity for personalized medicine.
Bile duct cancers may harbor a molecular alteration for which a targeted treatment might be available. Specific examples include Immunotherapy using a checkpoint inhibitor for deficient DNA mismatch repair/microsatellite instability-high (dMMR/MSI-H) or high level of tumor mutational burden (TMB), pemigatinib for fibroblast growth factor receptor 2 (FGFR2) gene alterations, Ivosidenib for isocitrate dehydrogenase (IDH) mutations, a tropomyosin receptor kinase (TRK) inhibitor for those with TRK fusion-positive cancers and the combination of a BRAF and mitogen-activated extracellular kinase (MEK) inhibitor for those with BRAF V600E mutations.
Several ongoing trials (such as NCI MATCH and TAPUR trials) are using next-generation sequencing (NGS) to identify molecular alterations in the tumors of patients with refractory cancers that may potentially match molecularly targeted therapies. Bile duct cancers has multiple molecular alterations, many of which are potential targets for available specific inhibitors.
Medical oncologists are expected to be familiar with the known molecular alterations in patients with bile duct cancers and how to address them through personalized Medicine. Medical oncologists and especially GI medical oncologists would benefit from becoming familiar with ongoing clinical trials and how they address molecular alterations, novel therapies or their combinations in first line or subsequent therapies in patients with bile duct cancer.
In Summary, this topic is expected to provide an 1) overview of the status of targeted therapy and immunotherapy in bile duct cancer, 2) discuss the ongoing clinical trials that address molecular profiling role in bile duct cancer and reviewing current caveats and future steps. 3) Provide insight in future directions in the field of bile ducts cancer management that would help and guide physician and scientists in their future research planning and goals.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
The prognosis of patients with biliary tract cancers is poor and most patients are diagnosed with advanced stages where treatment intent’s is typically palliative. In those patients, subsequent therapeutic options after progression on first line chemotherapy are limited. In recent years, the landscape of treatment of bile duct cancers has witnessed several changes and several novel treatment targets have been identified. Molecular profiling is now recommended and represents an opportunity for personalized medicine.
Bile duct cancers may harbor a molecular alteration for which a targeted treatment might be available. Specific examples include Immunotherapy using a checkpoint inhibitor for deficient DNA mismatch repair/microsatellite instability-high (dMMR/MSI-H) or high level of tumor mutational burden (TMB), pemigatinib for fibroblast growth factor receptor 2 (FGFR2) gene alterations, Ivosidenib for isocitrate dehydrogenase (IDH) mutations, a tropomyosin receptor kinase (TRK) inhibitor for those with TRK fusion-positive cancers and the combination of a BRAF and mitogen-activated extracellular kinase (MEK) inhibitor for those with BRAF V600E mutations.
Several ongoing trials (such as NCI MATCH and TAPUR trials) are using next-generation sequencing (NGS) to identify molecular alterations in the tumors of patients with refractory cancers that may potentially match molecularly targeted therapies. Bile duct cancers has multiple molecular alterations, many of which are potential targets for available specific inhibitors.
Medical oncologists are expected to be familiar with the known molecular alterations in patients with bile duct cancers and how to address them through personalized Medicine. Medical oncologists and especially GI medical oncologists would benefit from becoming familiar with ongoing clinical trials and how they address molecular alterations, novel therapies or their combinations in first line or subsequent therapies in patients with bile duct cancer.
In Summary, this topic is expected to provide an 1) overview of the status of targeted therapy and immunotherapy in bile duct cancer, 2) discuss the ongoing clinical trials that address molecular profiling role in bile duct cancer and reviewing current caveats and future steps. 3) Provide insight in future directions in the field of bile ducts cancer management that would help and guide physician and scientists in their future research planning and goals.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.