At the 2025 Annual Cholangiocarcinoma Foundation Conference, a working group that included co-chairs Anna Saborowski and Gregory Lesinski, as well as Funda Meric-Bernstam, Chiara Braconi, Jesper Andersen, Teresa Macarulla, Dan Duda, Katie Kelley, Mitesh Borad, Nilo Azad, Pedro Rodrigues, Tian Tian, Pilar Acedo, and Sarah Wang, presented on resistance to systemic therapies, validation of molecular biomarkers, and challenges in translation into clinical trials. Another working group comprised of co-chairs Luke Boulter and Sumera I. IIyas, as well as Ben Stanger, Laura Fouassier, Rory Smoot, Greg Gores, Mark Yarchoan, Matias Avila, Monique Verstegen, Nabeel Bardeesy, Silvia Affo, Rocio Macias, Tim Greten, Elisa Lozano, and George Riddle, presented on the tumor microenvironment phenotype, carcinogenesis, therapeutic resistance, and different therapies for cholangiocarcinoma (CCA).
The translation of scientific discoveries into therapeutic innovations is reshaping treatment landscapes. RNA-based therapies, bispecific antibodies, and cell-based treatments are addressing diseases once considered untreatable. In oncology, next-generation inhibitors and immunotherapies, such as CAR T-cells, have demonstrated remarkable success in overcoming resistance and improving patient survival. Preclinical models integrating tumor microenvironment components and big data analytics are refining drug pipelines and enhancing treatment durability. Advances in drug delivery systems, such as nanoparticle-based carriers, are increasing the precision and safety of therapeutic interventions.
Translational science serves as the critical bridge between basic research and clinical application, transforming laboratory discoveries into viable diagnostics, therapeutics, and preventive strategies. Recent advancements in this field have accelerated the development of precision medicine, particularly in oncology and chronic diseases, where understanding disease mechanisms at the molecular level is key to improving outcomes. A cornerstone of translational science is the application of multi-omics approaches, which include genomics, transcriptomics, proteomics, and metabolomics to uncover the molecular underpinnings of disease. These technologies enable researchers to identify biomarkers, understand disease heterogeneity, and stratify patients into subgroups most likely to benefit from targeted therapies. Furthermore, the integration of multi-omics data has revealed actionable genetic alterations, such as FGFR fusions and mutations, leading to the development of highly specific inhibitors for CCA such as tinengotinib.
Biomarker discovery remains essential for personalized medicine, helping identify patients likely to benefit from specific treatments. Advances in proteomics, transcriptomics, and metabolomics have highlighted dynamic biomarkers like circulating tumor DNA, which offer noninvasive diagnostic tools and real-time disease monitoring. Multimodal biomarker panels combining genetic and protein-level data are improving diagnostic accuracy and treatment predictions, with ongoing clinical trials ensuring validation across diverse populations.
Recent advancements in scientific discovery have unveiled groundbreaking insights into the mechanisms of disease and the development of innovative therapeutic strategies. The exploration of molecular pathways, biomarker identification, and novel drug targets continues to push the boundaries of modern medicine, particularly in the context of precision oncology and chronic disease management. Through multi-omics analyses and high-throughput sequencing, scientists have uncovered critical genetic alterations such as FGFR, KRAS, and HER2 mutations that drive disease progression. Precision therapies targeting these pathways provide safer and more effective alternatives to conventional treatments. Spatial and single-cell technologies further enhance research, offering insights into tumor microenvironments and cellular interactions critical for combination therapies addressing both intrinsic and extrinsic disease factors.
Advances in three-dimensional organoid models and patient-derived xenografts are also further enhancing translational research by creating systems that closely mimic human disease. These models allow for the testing of novel therapies in a preclinical setting, providing valuable insights into drug efficacy and resistance mechanisms. By combining these tools with computational modeling and artificial intelligence, researchers can accelerate the pipeline from discovery to clinical trials.
The shift toward patient-centered research is a defining feature of modern translational science. Incorporating patient-reported outcomes and real-world data into clinical studies has significantly improved the understanding of treatment efficacy and quality of life. For instance, the adoption of PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) has allowed researchers to capture symptoms directly from patients, leading to a more accurate assessment of drug tolerability.
Translational science is bridging the gap between laboratory discoveries and clinical applications, driving transformative advancements in diagnostics and therapeutics. Cutting-edge technologies like multi-omics analyses, spatial approaches, and preclinical modeling are uncovering the complexities of disease progression and therapeutic resistance. These breakthroughs, coupled with the validation of biomarkers and innovative delivery systems, are enabling the development of tailored treatments that improve patient outcomes. Continued collaboration across disciplines and patient-centered approaches will be crucial for sustaining innovation and delivering meaningful healthcare solutions worldwide.
Saborowski A, Lesinski G. WG5-Science (Translational). Presented at: 2025 Annual Cholangiocarcinoma Foundation Conference. April 9-11, 2025; Salt Lake City, UT.
Boulter L, IIyas SI. WG4-Science (Discovery). Presented at: 2025 Annual Cholangiocarcinoma Foundation Conference. April 9-11, 2025; Salt Lake City, UT.
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