Therapeutic discovery for cholangiocellular carcinoma

Introduction

Cholangiocarcinoma (CCA) is one of the deadliest cancers comprising a heterogeneous cluster of malignancies that are distinct from hepatocellular carcinoma (HCC) and can emerge at any point in the biliary tree. While not very common, CCA is responsible for 2% of cancer-related deaths worldwide annually, and this number is rising.

Incidence and Diagnosis

The incidence of CCA in European countries is increasing rapidly, ranging from 1 to more than 4 cases per 100,000. CCA is mostly diagnosed very late, resulting in aggressive disease progression, poor treatment response, and a dismal prognosis with a median survival of less than 2 years.

Treatment Options

Curative hepatic resection is an option in 10-30% of cases and is mostly linked to recurrence within 12 months in over 50% of patients. For most patients, diagnosis will occur when the disease is already too advanced, and the only options available are:

1. Chemotherapies
2. Palliative care

Current Standard of Care

The current standard-of-care for CCA is unsatisfactory, with very limited efficacy and adverse effects. Recently approved second-line therapeutics slightly improve outcomes but are only suited to a small subset of CCA patients. Thus, there is a major unmet medical need for novel therapeutic strategies to improve patient outcomes.

Research Objectives

Based on a robust data package obtained in a panel of CCA models within ERC HEPCIR, we will explore the use of a novel class of compounds exploiting a unique and differentiated first-in-class mechanism of action. We aim to validate their efficacy in vivo as a first-line therapeutic for CCA.

Methodology

Proof-of-concept studies will be performed in state-of-the-art patient-derived models combined with scRNASeq and proteomics. The data obtained will serve as a pre-IND data package for this indication.

Collaboration and Impact

An established collaboration with a pharma partner will ensure fast-track completion of the preclinical development towards IND. Collectively, ERC PoC CANDY will deliver completed proof-of-concept for a novel therapeutic approach for CCA, which has the potential to transform patient care.