# Targeting Biliary Tract Cancers with Antibody–Drug Conjugates: Advances in Molecular Targets and Rational Combinations

## TL;DR

This review discusses how antibody-drug conjugates may offer a more targeted treatment for biliary tract cancers, which are hard to treat due to late diagnosis and limited drug effectiveness.

## Contribution

The paper provides a comprehensive overview of ADCs in biliary tract cancers, focusing on molecular targets and combination therapies.

## Key findings

- ADCs combine antibodies with potent drugs to target cancer cells more effectively.
- Clinical and preclinical studies show encouraging preliminary results for ADCs in biliary tract cancers.
- Combining ADCs with immunotherapy or targeted drugs is being explored to improve treatment outcomes.

## Abstract

Biliary tract cancers are difficult to treat because they are often diagnosed late and because many drugs cannot effectively reach or control the tumor. Antibody–drug conjugates are a new type of targeted medicine that links an antibody, which can recognize a marker on cancer cells, to a highly potent anti-cancer drug. This design aims to deliver the drug more directly to tumor cells and reduce damage to normal tissues. In this review, we summarize which tumor markers are being tested for these medicines in biliary tract cancers, what clinical studies have shown so far, and the explorations related to the combination of antibody–drug conjugates with other treatment methods (such as immunotherapy or targeted drugs). Our goal is to provide an updated and practical overview that helps researchers and clinicians understand current progress, identify promising directions, and guide future study design in this rapidly developing field.

Antibody–drug conjugates (ADCs), an emerging targeted treatment method, are designed to couple the tumor selectivity of monoclonal antibodies with the cytotoxic potency of small-molecule payloads, thereby offering an accurate approach for biliary tract cancers (BTCs). BTC is characterized by typical molecular heterogeneity, a desmoplastic stroma, and an immune-suppressive microenvironment, which together limit the efficacy of conventional chemotherapy and weaken responses to immunotherapy in unselected patients. The demand for drugs that can improve the survival rate of BTC patients has not yet been met. The evaluation of ADC therapy for BTC has become a focus of extensive clinical and preclinical research, and encouraging preliminary results have been achieved. In this review, we comprehensively summarize the increasing body of evidence regarding the application of ADCs in BTC relative trials. Starting with a brief discussion of the functional principles of ADCs, we summarize the trials of different designs of ADCs in BTC, as well as the relevant clinical data related to ADC-based combination therapy regimens.