Is there anything new that can be done to treat cholangiocarcinoma?

If you have been told you have cholangiocarcinoma, you might be wondering if there are any new ways to treat this disease. The good news is that you have a number of choices, such as surgical resection, FGFR inhibitors, and PARP inhibitors. But you should also know that these methods of treatment come with a few possible risks.

Cholangiocarcinoma is rare cancer that starts in the bile duct's epithelial cells. It can be localized or spread out, affecting different parts of the biliary tree in different ways. The only treatment that might work is surgical resection.

Cholangiocarcinoma is diagnosed based on the patient's history, the results of a physical exam, and the results of tests done in a lab. After resection, patients are looked at to find out how they will do. Most of the time, surgical resection works. But even after resection, cancer can come back.

Depending on where the tumor is, there are different ways to remove it. Most of the time, liver resection is used to treat intrahepatic cholangiocarcinomas. For distal or perihilar cholangiocarcinomas, the bile duct needs to be cut out. Hepatic resection patients should have liver drainage before their surgery. Partially removing the liver is often done along with removing the entire caudate lobe.

Most of the time, partial hepatectomy, bile duct resection, and a large amount of liver removal are used to treat perihilar cholangiocarcinomas. Overall survival is shorter for people with distal and perihilar cholangiocarcinomas. They also have a higher rate of nerve invasion around the nerves.

Targeting FGFR inhibitors as a way to treat cholangiocarcinoma is a new approach. Traditional treatments for this disease aren't likely to work, but targeted therapies may be able to help.

Several FGFR inhibitors are being tested in people right now. One of these is debit-1347. Another is pemigatinib. Debio-1347 is a strong multikinase inhibitor that can be taken by mouth. It has been shown to go after FGFR-deregulated tumors in a specific way. In phase II trials, people with advanced cholangiocarcinoma and FGFR2 rearrangements were helped by pemigatinib.

The US Food and Drug Administration (FDA) approved pemigatinib in April 2020. It is a small-molecule FGFR1-3 inhibitor that can be taken by mouth. March 2021 is set aside for approval from the European Commission. This drug has also been tried out for metastatic cholangiocarcinoma in a phase II trial.

Infigratinib, another FGFR inhibitor, is being looked at as a first-line treatment for FGFR2-fusions in cholangiocarcinoma that can't be removed. A Phase III study is currently going on.

Pemigatinib has been shown to be an inhibitor of FGFR1 and FGFR2 that is very strong and selective. With its strong affinity for both FGFR1 and FGFR2 and its large network of hydrogen bonds, it could be used to treat cancers that are caused by FGFR.

PARP inhibitors are a new type of chemotherapeutic drug that shows promise in the treatment of solid tumors. The Food and Drug Administration has approved three PARP inhibitors so far, and a number of other drugs are in the works. They work well for people with cancers caused by BRCA mutations. Even though the clinical results were good, more research is needed to find out which patients may benefit the most from this therapy. In the meantime, these agents are being used in a number of clinical trials to test new drug combinations.

Poly ADP-ribose polymerase (PARP) is an enzyme that is very important for fixing single-strand breaks in DNA. When the BRCA gene is changed, the genome becomes unstable. This makes the homologous recombination (HR) pathway useless. By stopping the cells from being able to fix DSBs, PARP inhibition may be able to reduce the number of mutations in HRD-related tumors.

Early clinical and preclinical data suggest that inhibiting PARP may also be able to fix the deficiency caused by an IDH1 mutation. Because of these mutations, isocitrate is changed into 2-hydroxyglutarate, which helps tumor cells grow. Because of this, the PI3k pathway, which is a common way for tumors to grow, is often always turned on.

The neurotrophic tyrosine receptor kinases (NTRK) genes are very important for how nerve cells grow and stay healthy. They also play a role in the growth of some types of cancer. When one of these genes is moved around, it causes a fusion, which is then expressed as a chimeric protein.

NTRK fusions are found in many different types of tumors, such as sarcomas, colon, secretary breast carcinoma, non-small cell lung cancer, cholangiocarcinoma, and melanoma. But they aren't very common. It is hard to tell if a patient's tumor has a rearranged NTRK gene because of this.

Screening for a rearranged NTRK can be done in a number of ways. Next-generation sequencing is what most oncologists like to use. But there are times when IHC is better.

NTRK fusions have been found in people with many different types of cancer, but most of these people have non-small cell lung cancer or sarcoma. NTRK fusion tumors fall into two main categories: rare and common.