Abstract
Intrahepatic cholangiocarcinoma, a malignancy of the intrahepatic bile ducts, is the second most common primary liver malignancy and has been rising in incidence over the past several decades. Given its poor prognosis and diagnosis at a late stage, novel therapies are urgently needed to improve outcomes. Intrahepatic cholangiocarcinoma harbors a high rate of targetable mutations, spurring an increased interest in drug development in this disease. FGFR2 gene rearrangements occur in approximately 10–16% of these tumors and this underscores the importance of next generation sequencing in this population. There are now several FGFR inhibitors in development, and these agents may help improve outcomes for these patients. However, both primary and secondary resistance remain a challenge.
Plain language summary
Intrahepatic cholangiocarcinoma is a type of cancer that occurs in the liver. This type of cancer is becoming increasingly common over the past several decades. New types of treatments are urgently needed to improve outcomes in this disease. Intrahepatic cholangiocarcinomas often have changes in their genetic makeup that may be used to help treat the disease. Changes in the FGFR2 occur in 10–16% of these tumors. There are now several US FDA approved medications that can help target this change in the tumor. However, these drugs may lose effectiveness after several months as the tumor may become resistant to the medication. There are new drugs currently in development that may be able to overcome this problem.