Novel targeted treatment options for advanced cholangiocarcinoma

ABSTRACT

Introduction: Surgical resection remains the mainstay of potentially curative treatment in the early stages of cholangiocarcinoma, whereas for the advanced stage, systemic chemotherapeutics and experimental targeted therapies are the primary treatment options. The molecular heterogeneity of the tumor is based on location, liver dysfunction, and relative rarity of the disease and confers challenges for clinical trial enrollment. The advancements in the understanding of molecular pathogenesis of cholangiocarcinoma have led to the development of targeted therapies that are currently being evaluated in the clinical trials.

Areas covered: This review summarizes the current understanding and future directions of targeted therapeutic options in the management of advanced cholangiocarcinoma.

Expert opinion: Advanced cholangiocarcinoma has a dismal prognosis; improved understanding of the molecular pathogenesis and advancements in development of targeted therapy offers hope that we may improve outcomes in this rare, but highly lethal cancer. Among the newly discovered molecular alterations, targeting FGFR2 fusions, IDH1/2 mutations and HER2 receptors hold great promise for improving the future management of cholangiocarcinoma. Immunotherapy in combination with targeted agents and chemotherapy may improve outcomes. In addition, drugs targeting the MEK, EGFR, KRAS, BRAF, and ROS1 pathways and neo-angiogenesis may also provide new horizons in the management of cholangiocarcinoma.

KEYWORDS:

• Targeted therapy
• cholangiocarcinoma
• FGFR
• IDH
• gemcitabine

Article highlights

• Most of the data on the chemotherapy regimens in advanced cholangiocarcinoma are primarily based on phase II trials except for gemcitabine and cisplatin combination, which remains the standard of care in advanced cholangiocarcinoma.

• Understanding the key signaling pathways and genetic alterations in cholangiocarcinoma play a prominent role in identifying novel drug targets.

• Among the newly discovered molecular alterations, targeting FGFR2 fusions, IDH1/2 mutations, and HER2 receptors hold great promise for improving the future management of advanced cholangiocarcinoma.

• Advanced cholangiocarcinoma patients should be encouraged to participate in ongoing clinical trials.

Declaration of interest

R Kim has received honoraria from Lilly, BMS and Bayer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer is a Consultant for AstraZeneca and Bayer. Other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded