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Published on: September 30, 2021
Molecular Targets in Cholangiocarcinoma
Colm J O'Rourke1, Patricia Munoz-Garrido1, Jesper B Andersen1
1Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract:
Cholangiocarcinoma (CCA) encompasses a heterogeneous collection of malignancies for which diagnostic biomarkers are lacking and population screening is infeasible because of its status as a rare disease. Coupled with high postsurgical recurrence rates among the minority of patients diagnosed at resectable stages, systemic clinical management will inevitably be required for the majority of patients with CCA with recurrent and advanced disease. In this review, we discuss the therapeutic potential of different classes of molecular targets at various stages of development in CCA, including those targeted to the tumor epithelia (oncogenic, developmental, metabolic, epigenomic) and tumor microenvironment (angiogenesis, checkpoint regulation). Furthermore, we discuss the successes and failures of CCA-targeted therapies, emphasizing key lessons learned that should pave the way for future molecular target evaluation in this uncommon yet bona fide target-rich disease.
Insights
Cholangiocarcinoma (CCA) lacks diagnostic biomarkers, necessitating systemic therapies for advanced disease. This review explores molecular targets and therapeutic strategies for CCA, offering insights for future drug development.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Cholangiocarcinoma (CCA) is a rare cancer with limited diagnostic tools and high recurrence rates.
- Most patients require systemic treatment due to advanced or recurrent disease.
- Current therapeutic strategies for CCA are insufficient.
Purpose of the Study:
- To review the therapeutic potential of molecular targets in CCA.
- To analyze successes and failures of CCA-targeted therapies.
- To provide lessons for future molecular target evaluation in CCA.
Main Methods:
- Literature review of molecular targets and therapies for CCA.
- Analysis of targets in tumor epithelia (oncogenic, developmental, metabolic, epigenomic).
- Evaluation of targets in the tumor microenvironment (angiogenesis, checkpoint regulation).
Main Results:
- Various molecular targets are under investigation for CCA.
- Therapeutic strategies targeting tumor epithelia and microenvironment show promise.
- Past clinical trials have yielded both successes and failures.
Conclusions:
- CCA presents a target-rich landscape for molecular therapies.
- Understanding past therapeutic outcomes is crucial for future drug development.
- Further research into novel molecular targets and combination therapies is warranted for CCA.
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