Integration of circulating tumor DNA in biliary tract cancer: the emerging landscape

Sep 21, 2026

Uploaded by Sage

Precision medicine reshapes cancer care by using molecular profiling to guide diagnosis, prognosis, and treatment. For biliary tract cancers (BTCs), obtaining adequate tissue tumor DNA is frequently constrained by anatomical and sample-quality challenges, limiting genomic analysis. Circulating tumor DNA (ctDNA) offers a noninvasive alternative using plasma and bile, supporting high mutation detection, isolating actionable alterations, and enabling concordance with tissue. Serial ctDNA measurements help assess clonal evolution, recurrence monitoring, prognostication, and emerging resistance mechanisms, supporting clinical integration and ongoing ctDNA surveillance after curative intent.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

ctDNA biology and detection rationale

Sequencing and assay limitations

Clinical applications and future directions

REVIEW Integration of circulating tumor DNA in biliary tract cancer: the emerging landscape Joy A Awosikaa, Cecilia Mongea and Tim F Greten* , a a Gastrointestinal Malignancies Section, Thoracic & GI Malignancies Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA ABSTRACT Precision medicine has emerged as a cornerstone in cancer treatment revolutionizing our approach across malignancies. Molecular profiling of biliary tract cancers (BTCs) has changed the treatment landscape positively by prolonging survival in an aggressively fatal malignancy in its advanced stages. The acquisition of tissue tumor DNA for genomic analysis in BTC is often anatomically challenging, limited by quantity and quality. In response, ctDNA has emerged as a noninvasive means of molecular profiling. The utility of both plasma and bile ctDNA has been explored in several studies demonstrating the high mutation detection rates and the ability to isolate targetable mutations when present. In addition, the concordance between plasma and tissue DNA provides validity in utilizing ctDNA results to infer treatment decisions. Analysis of ctDNA in BTC has also provided prognostic information and facilitated evaluation of clonal evolution with ease of serial measurements. Insight into novel mechanisms of resistance to targeted therapies are being uncovered in ctDNA. As research endeavors continue to deepen our understanding in the field particularly in the space of ctDNA surveillance after curative intent, the tremendous progress made so far has enabled integration of ctDNA into the clinical practice of BTCs. PLAIN LANGUAGE SUMMARY The approach to treating cancer is changing remarkably by customizing treatments to fit each patient’s unique cancer. Your doctor can determine the best treatment for you by looking at the genes of that cancer and if there is a drug available that targets that gene. Identifying these genes is especially helpful for a tough cancer such as biliary tract cancer (BTC), which is hard to treat and often deadly. Getting enough cancer tissue to test can be difficult because of where the cancer is located and how much tissue is available. ctDNA is tiny pieces of cancer’s genetic material that float in the blood and testing ctDNA is easier and less invasive than taking samples directly from the tumor. Studies are helping us understand ctDNA better and how to use it in BTC treatment. Results from ctDNA tests are reliable enough to help doctors decide on treatments. It helps track how the cancer changes over time and can spot new changes that might affect treatment. Using ctDNA, doctors can better follow and treat BTC, adjusting treatments as needed to improve patient outcomes. ARTICLE HISTORY Received 9 May 2024 Accepted 9 September 2024 KEYWORDS biliary tract cancer; cell free DNA; cholangiocarcinoma; circulating tumor DNA; liquid biopsy; precision medicine 1. Introduction The advancements made in the genomic landscape of various cancers has revolutionized our understanding of tumor biology, provided targeted treatment options, aided in diagnosis and prognosis and introduced an additional tool in the surveillance of cancer patients. The demonstration of circulating tumor DNA (ctDNA) was an observation first made as far back as 1977 recognizing that cancer patients carried cell free DNA in their peripheral blood [1] . The mechanism of ctDNA entry into the bloodstream is still an area of research but has been linked to release from apoptotic or necrotic tumor cells, living and circulating tumor cells [2–5] . Significant strides in refining sequencing methodologies have propelled advancements in the assays employed in ctDNA testing. While considerable progress has been made in bolstering the sensitivity and specificity of these assays, certain limitations persist. Challenges include false-negative results, as well as reduced sensitivity in detectin

FAQs

Why is ctDNA useful in biliary tract cancer when tissue testing is difficult?

Tissue tumor DNA collection for genomic analysis is often anatomically challenging and limited by quantity and quality. ctDNA enables noninvasive molecular profiling using plasma or bile, reducing reliance on difficult tissue sampling.

How do plasma and tissue ctDNA results support treatment decisions?

Studies evaluate mutation detection from plasma and bile ctDNA and examine concordance between ctDNA and tissue DNA. This relationship supports using ctDNA findings to infer treatment-relevant information.

What role does ctDNA play beyond mutation detection in BTC?

ctDNA analysis provides prognostic information, supports evaluation of clonal evolution through serial measurements, and can help detect and monitor recurrent or residual disease. It also helps uncover mechanisms of resistance to targeted therapies.

Sep 21, 2026

Uploaded by Sage