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Review
. 2024 Sep 30;16(19):3345.
doi: 10.3390/cancers16193345.

Antibody-Drug Conjugates and Their Potential in the Treatment of Patients with Biliary Tract Cancer

Shaun Alexander  1 , Umair Aleem  1 , Timothy Jacobs  2 , Melissa Frizziero  1 , Victoria Foy  1 , Richard A Hubner  1 , Mairéad G McNamara  3
Affiliations
Review

Antibody-Drug Conjugates and Their Potential in the Treatment of Patients with Biliary Tract Cancer

Shaun Alexander et al. Cancers (Basel). .

Abstract

Background: Biliary tract cancers (BTCs) are aggressive in nature, often presenting asymptomatically until they are diagnosed at an advanced stage. Surgical resection or liver transplantation are potential curative options. However, a large proportion of patients present with incurable locally advanced or metastatic disease and most of these patients are only eligible for palliative chemotherapy or best supportive care. More recently, targeted therapies have proven beneficial in a molecularly selected subgroup of patients with cholangiocarcinoma who have progressed on previous lines of systemic treatment. However, only a minority of patients with BTCs whose tumours harbour specific molecular alterations can access these therapies. Methods: In relation to ADCs, studies regarding use of antibody-drug conjugates in cancer, particularly in BTCs, were searched in Embase (1974 to 2024) and Ovid MEDLINE(R) (1946 to 2024) to obtain relevant articles. Examples of current clinical trials utilising ADC treatment in BTCs were extracted from the ClinicalTrials.gov trial registry. Conclusions: Overall, this review has highlighted that ADCs have shown encouraging outcomes in cancer therapy, and this should lead to further research including in BTCs, where treatment options are often limited. The promising results observed with ADCs in various cancers underscore their potential as a transformative approach in oncology, warranting continued exploration and development and the need for education on the management of their specific toxicities. By addressing current challenges and optimising ADC design and application, future studies could potentially improve treatment outcomes for patients with BTCs and beyond, potentially in both early and advanced stage settings.

Keywords: anti-HER2; antibody–drug conjugate; biliary tract cancer; payload; targeted therapy.

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Conflict of interest statement

SA. received speaker honoraria from Novartis. MMN. received research grant support from Astra Zeneca, Servier, Ipsen, and NuCana. She received travel and accommodation support from Bayer and Ipsen and speaker honoraria from Pfizer, Ipsen, NuCana, Mylan, and AAA. She served on advisory boards for Celgene, Ipsen, Sirtex, Baxalta, Incyte, and Astra Zeneca, all outside of the scope of this work. R.H. served on advisory boards for Roche, BMS, Eisai, Celgene, Beigene, Ipsen, and BTG. He received speaker fees from Eisai, Ipsen, Mylan, PrimeOncology, and received travel and educational support from Bayer, BMS, and Roche, all outside of the scope of this work. MF. Received honoraria and travel and accommodation support from AAA/Novartis and travel and accommodation support from Roche, all are outside the scope of this work. VF-has received travel and educational support from Servier, Ipse, and AstraZeneca. U.A and T.J declare no conflicts of interest.

Figures

Figure 1
Figure 1
Diagram highlighting prevalence of common molecular alterations following genomic sequencing in BTC based on anatomical location and potential targeted therapies. Abbreviations: iCCA, intrahepatic cholangiocarcinoma; GBC, gallbladder cancer; eCCA; extrahepatic cholangiocarcinoma [12,29,30,31,32,33].
Figure 2
Figure 2
Structure and mechanism of action of ADC. (A) Humanised monoclonal antibody (mAb), (B) Linker at conjugation site (green), (C) Cytotoxic payload, (D) Antigen-binding sites (E) Target binding to cell-surface antigen, (F) Internalisation of ADC–antigen complex, (G) Lysosomal deconjugation, (H) Active cytotoxic payload release, (I) DNA/microtubule disruption, (J) Cell death [36,48,49].
See this image and copyright information in PMC

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