Cholangiocarcinoma: cfDNA Monitoring Emerges Alongside FGFR2 and IDH1 Targeted Therapies
This comprehensive review covered breakthroughs in cholangiocarcinoma including four newly approved targeted therapies (three for FGFR2 fusions, one for IDH1 variants) and the emergence of cell-free DNA assays for disease detection and monitoring. The characterisation of distinct immune microenvironments including immune-desert tumours has important implications for companion diagnostic strategies and immunotherapy patient selection.
The original study
Cholangiocarcinoma - novel biological insights and therapeutic strategies.
- Authors
- Ilyas SI, Affo S, Goyal L, Lamarca A, Sapisochin G, Yang JD, et al.
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Review, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- PMID
- 37188899
Original abstract
In the past 5 years, important advances have been made in the scientific understanding and clinical management of cholangiocarcinoma (CCA). The cellular immune landscape of CCA has been characterized and tumour subsets with distinct immune microenvironments have been defined using molecular approaches. Among these subsets, the identification of 'immune-desert' tumours that are relatively devoid of immune cells emphasizes the need to consider the tumour immune microenvironment in the development of immunotherapy approaches. Progress has also made in identifying the complex heterogeneity and diverse functions of cancer-associated fibroblasts in this desmoplastic cancer. Assays measuring circulating cell-free DNA and cell-free tumour DNA are emerging as clinical tools for detection and monitoring of the disease. Molecularly targeted therapy for CCA has now become a reality, with three drugs targeting oncogenic fibroblast growth factor receptor 2 (FGFR2) fusions and one targeting neomorphic, gain-of-function variants of isocitrate dehydrogenase 1 (IDH1) obtaining regulatory approval. By contrast, immunotherapy using immune-checkpoint inhibitors has produced disappointing results in patients with CCA, underscoring the requirement for novel immune-based treatment strategies. Finally, liver transplantation for early stage intrahepatic CCA under research protocols is emerging as a viable therapeutic option in selected patients. This Review highlights and provides in-depth information on these advances.