Opinion Article - Journal of Molecular Oncology Research (2025) Volume 9, Issue 2
Harnessing circulating tumor dna (ctdna) for precision oncology: Advances and challenges
Fabrice Andre*
Department of Medical Oncology, Gustave Roussy Institute, France
- *Corresponding Author:
- Fabrice Andre
Department of Medical Oncology, Gustave Roussy Institute, France
E-mail: fabrice.andre@gustaveroussy.fr
Received: 01-May-2025, Manuscript No. AAMOR -25-166707; Editor assigned: 02-May-2025, PreQC No. AAMOR -25-166707(PQ); Reviewed: 18-May-2025, QC No. AAMOR -25-166707; Revised: 22-May-2025, Manuscript No. AAMOR -25-166707(R); Published: 29-May-2025, DOI: 10.35841/ aamor-9.2.288
Citation: : Andre F. Harnessing circulating tumor DNA (CTDNA) for precision oncology: Advances and challenges. J Mol Oncol Res. 2025;9(2):288.
Introduction
Cancer management has witnessed a paradigm shift with the advent of minimally invasive diagnostic techniques, prominently led by the analysis of circulating tumor DNA (ctDNA). ctDNA refers to small fragments of DNA shed by tumor cells into the bloodstream, representing a non-invasive biomarker that holds significant promise in molecular oncology research. The ability to detect and analyze ctDNA enables real-time insights into tumor genetics, facilitating early diagnosis, treatment monitoring, and personalized therapy decisions.
Unlike traditional tissue biopsies, which are invasive and limited by tumor heterogeneity and sampling constraints, ctDNA analysis provides a comprehensive snapshot of the tumor’s molecular landscape. This dynamic approach supports the evolving needs of precision oncology by capturing tumor evolution and resistance mechanisms without repeated surgical interventions [1].
The Role of ctDNA in Early Cancer Detection and Diagnosis. One of the most compelling applications of ctDNA is in early cancer detection. Sensitive molecular assays, such as digital PCR and next-generation sequencing (NGS), allow detection of tumor-specific mutations, methylation patterns, and other genetic alterations in blood samples. Early detection through ctDNA can significantly improve patient outcomes by enabling timely intervention before clinical symptoms or radiological signs emerge. Additionally, ctDNA profiling aids in diagnosing cancers that are difficult to biopsy or located in inaccessible sites. By providing molecular information non-invasively, ctDNA analysis can complement conventional diagnostic workflows and reduce the risks associated with tissue biopsies [2].
Monitoring Treatment Response and Detecting Resistance. In molecular oncology, the monitoring of ctDNA levels offers valuable insights into therapeutic efficacy. Changes in ctDNA concentration correlate with tumor burden, providing a sensitive measure to assess treatment response earlier than imaging techniques. Declining ctDNA levels post-therapy often predict favorable outcomes, whereas rising levels can signal disease progression or relapse. Moreover, ctDNA analysis can uncover emerging resistance mutations during targeted therapies or immunotherapies. By identifying these genetic alterations promptly, clinicians can modify treatment regimens to overcome resistance, ultimately improving patient survival and quality of life [3].
Technical Advances and Integration in Clinical Practice. Recent technological advances have enhanced the sensitivity and specificity of ctDNA detection.. Techniques like ultra-deep sequencing and error-corrected NGS allow for the detection of rare mutant alleles amid a background of normal DNA, overcoming challenges posed by the low abundance of ctDNA.
Clinical trials have increasingly incorporated ctDNA testing to guide treatment decisions, especially in lung, colorectal, and breast cancers. The integration of ctDNA analysis into routine clinical practice promises to streamline cancer care, reduce invasive procedures, and personalize treatment approaches. Challenges and Future Perspectives. Despite its transformative potential, ctDNA analysis faces several limitations. The quantity of ctDNA varies widely between patients and tumor types, sometimes leading to false negatives. Standardization of pre-analytical and analytical protocols remains a critical hurdle to ensure reproducibility and accuracy across laboratories [4].
Additionally, interpreting ctDNA data requires sophisticated bioinformatics tools and clinical expertise to distinguish clinically relevant mutations from benign alterations. Ethical issues related to genetic data privacy and patient consent also necessitate careful consideration as ctDNA testing becomes widespread. Future directions in molecular oncology research include combining ctDNA with other circulating biomarkers such as circulating tumor cells (CTCs) and exosomes to achieve a holistic view of tumor biology. Advances in single-molecule sequencing and machine learning algorithms are expected to further improve detection sensitivity and clinical utility [5].
Conclusion
Circulating tumor DNA has emerged as a powerful tool in molecular oncology, offering minimally invasive access to tumor genetic information that can revolutionize cancer diagnosis, monitoring, and treatment personalization. While challenges remain in standardization and interpretation, ongoing technological innovations and clinical validations are rapidly advancing ctDNA from research settings to routine oncology practice. With continued multidisciplinary collaboration, ctDNA analysis is poised to become an integral component of precision oncology, ultimately improving outcomes for cancer patients worldwide.
References
- Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-24.
- Hirsch FR, Scagliotti GV, Mulshine JL, et al. Lung cancer: Current therapies and new targeted treatments. Lancet. 2017; 389:299-11.
- Kim JH, Kim HS, Kim BJ, et al. Prognostic impact of TTF-1 expression in non-squamous non-small-cell lung cancer: a meta-analysis. J Cancer. 2018; 9(22):4279-286.
- Chow SC, Gowing SD, Cools-Lartigue JJ, et al. Gram negative bacteria increase non-small cell lung cancer metastasis via toll-like receptor 4 activation and mitogen-activated protein kinase phosphorylation. Int J Cancer. 2015; 136(6):1341-350.
- Zhou H, Suo J, Zhu J, et al. Therapeutic relevance of human microbiota and lung cancer. Chin J Lung Cancer. 2019; 22(7):464-69.
- Apicella M, Corso S, Giordano S, et al. Targeted therapies for gastric cancer: failures and hopes from clinical trials. Oncotarge. 2017;8(34):57654-69.
- Pormohammad A, Ghotaslou R, Leylabadlo HE, et al. Risk of gastric cancer in association with Helicobacter pylori different virulence factors: A systematic review and meta-analysis. Microb Pathog. 2018;118:214-219.
- Posselt G, Backertv S, Wessler, et al. The functional interplay of Helicobacter pylorifactors with gastric epithelial cells induces a multi-step process in pathogenesis. Cell Commun Signal. 2013;77:11.
- Ostuni R, Kratochvill F, Murray PJ, et al. Macrophages and cancer: From mechanisms to therapeutic implications.Trends Immunol. 2015;36(4):229-39.
- Mantovani A, Sozzani S, Locati M, et al. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549-55.
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