The Role of Extracellular Genetic Materials in Cancer: From Diagnosis to Therapy

Cancer, a complex and multifaceted disease, continues to challenge the medical community. However, recent advancements in the understanding of extracellular genetic materials (EGMs) have opened new avenues for diagnosis, prognosis, and therapy. EGMs, including cell-free DNA (cfDNA), RNA, and DNA/RNA-related molecules, are released from cells into the extracellular region and body fluids, offering a valuable resource for non-invasive cancer monitoring.

Cell-Free DNA (cfDNA) and Cancer
One of the most studied EGMs is cfDNA, which can originate from various tissues and is influenced by different circumstances. The presence of cfDNA in the bloodstream has been associated with several pathological events, including cancer. The discovery of cfDNA in blood plasma by Mandel and Metais in 1948 has led to extensive research, particularly in its application in oncology.

cfDNA levels are higher in cancer patients compared to healthy individuals, and these levels correlate with tumor size and stage. The ability to detect tumor-specific mutations and epigenetic changes in cfDNA has made it a promising biomarker for cancer diagnosis, prognosis, and monitoring therapeutic responses. The Potential of cfDNA in Liquid Biopsy
Liquid biopsy, a non-invasive method that uses biological samples such as blood, has gained traction in cancer management. It allows for the detection of genetic alterations, providing insights into tumor heterogeneity and real-time monitoring of disease progression. The integration of next-generation sequencing (NGS) technology has enhanced the sensitivity and specificity of cfDNA analysis, enabling the early detection of rare tumor alleles and minimal residual disease (MRD).

The U.S. Food and Drug Administration (FDA) has approved several liquid biopsy tests based on cfDNA analysis for various cancers, highlighting its clinical utility in guiding treatment decisions and improving patient outcomes.

Beyond Diagnosis: cfDNA in Therapy and Prenatal Testing
In addition to its diagnostic applications, cfDNA has therapeutic potential. It can be used as a carrier for targeted therapy, delivering specific genetic material to cancer cells. Furthermore, cfDNA plays a crucial role in prenatal testing, allowing for the non-invasive detection of fetal genetic abnormalities early in pregnancy.

Challenges and Future Perspectives
Despite the promising applications of cfDNA and other EGMs in cancer, challenges remain. The mechanisms of cfDNA release, uptake, and interaction with target cells are not fully understood. Moreover, the heterogeneity of cfDNA and its dynamic nature in response to therapy necessitate further research to optimize its use in clinical practice.

In conclusion, EGMs, particularly cfDNA, offer a promising avenue for advancing cancer diagnosis, prognosis, and therapy. As our understanding of these materials deepens, their integration into personalized medicine will continue to evolve, ultimately improving patient care and outcomes in oncology.

Reference:
Koçana, C. Ç., Toprak, S. F., & Sözer, S. (2021). Extracellular genetic materials and their application in clinical practice. Cancer Genetics, 252, 48-63.