New Drugs for hepatobiliary Cancers - J of Hepatology - Jan.26

The treatment of hepatobiliary cancers, including hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is undergoing significant advancements with the development of novel drugs and therapeutic strategies. These developments are primarily categorized into two key strategies:

1. **Immune System Targeting Beyond Conventional Checkpoints**:

• Novel therapies are being developed to target immune checkpoints beyond the well-established ones like PD-1 and CTLA-4. This includes new antibodies aimed at alternative immune checkpoints and cytokines that regulate tumor immune responses.
• Combinations of these antibodies with already approved immunotherapy regimens are being investigated in Phase II and III clinical trials.
• Cellular therapies, such as chimeric antigen receptor (CAR)-T cells and tumor-infiltrating lymphocytes (TILs), are in early clinical testing for both HCC and BTC.
• Advances in antibody engineering have enabled the development of bispecific T-cell engagers, which are designed to enhance immune responses against tumors.

2. **Targeting Traditionally Undruggable or Novel Pathways**:

• New drugs are being developed to target pathways and molecules previously considered undruggable, such as PPAR-α, KRAS, histone deacetylase, and β-catenin.
• Antibody-drug conjugates (ADCs) targeting HER2 or nectin-4, which have shown success in other cancers, are being explored for BTC.

Additionally, these advances are influencing the treatment of less common liver cancer subtypes, such as sarcomatoid HCC and combined HCC-cholangiocarcinoma. Emerging genomic data and clinical experiences suggest that these rare cancers may be responsive to immune checkpoint inhibitors. Including these subtypes in clinical trials could accelerate the development of effective therapies.

In conclusion, the ongoing innovations in immunotherapy, cellular therapies, and targeted drug development are reshaping the treatment landscape for hepatobiliary cancers, offering new hope for improved outcomes in these challenging malignancies.