Extrachromosomal DNA (ecDNA): A Breakthrough in Cancer Biology

Biotechnology Cancer DNA GS3 Science&Technology

Why in News?

Recent studies published in Nature by the eDyNAmiC research group led by Stanford University challenge long-held beliefs about genetics and reveal ecDNA’s pivotal role in cancer progression and drug resistance.

Relevance for UPSC Exam

This topic is important for GS Paper III (Science and Technology, Health), particularly under:

  1. Biotechnology and Health: Advances in cancer research.
  2. Science and Society: Application of genomic research to improve healthcare.
  3. Ethical Issues: Balancing cutting-edge research with accessibility and equity in treatment.

What is ecDNA?

  • Definition: ecDNA is a small, circular DNA fragment that floats freely in the cell nucleus, distinct from the 23 pairs of chromosomes in human cells.
  • Formation: It arises due to errors in DNA replication or structural damage like chromothripsis (chromosomal shattering and rearrangement).
  • Prevalence: Detected in up to 40% of cancer cell lines and 17% of tumour samples, particularly in brain tumours, liposarcomas, and breast cancers.

Key Findings from the Studies

  1. Role in Cancer Growth:
    • ecDNA contains multiple copies of oncogenes (genes that cause cancer).
    • Unlike chromosomal DNA, ecDNA can move freely, interact, and amplify oncogene expression by up to four times.
  2. Genetic Inheritance Violation:
    • Mendel’s third law of independent assortment states that genes on different chromosomes are inherited randomly.
    • ecDNA violates this rule by being inherited in clusters, enabling cancer cells to preserve advantageous genetic traits over generations.
  3. Drug Resistance:
    • Cancer cells with ecDNA develop drug resistance due to rapid gene amplification and evolution.
  4. Vulnerability Identified:
    • ecDNA-dependent cancer cells heavily rely on the CHK1 protein to fix DNA damage.
    • Blocking CHK1 with a drug like BBI-2779 selectively kills these cancer cells, as shown in mice with stomach cancer.

Advantages of ecDNA Research

  1. Better Understanding of Cancer:
    • Helps unravel mechanisms of tumour growth and drug resistance.
  2. Targeted Treatments:
    • Drugs targeting ecDNA vulnerabilities offer hope for aggressive cancers like glioblastoma and ovarian cancer.
  3. Breakthrough in Genetics:
    • Challenges classical genetic theories and opens new avenues for research.

Challenges

  1. Implementation:
    • Translating lab findings into clinical treatments remains complex and time-consuming.
  2. Cost:
    • Developing ecDNA-specific drugs may be expensive, limiting accessibility.
  3. Ethical Concerns:
    • Managing genetic manipulation and treatment outcomes raises societal and regulatory challenges.

Way Forward

  1. Translational Research:
    • Speed up the transition from discovery to clinical trials for drugs like BBI-2779.
  2. Global Collaboration:
    • Foster international partnerships for ecDNA research.
  3. Public Awareness:
    • Educate stakeholders on the implications of ecDNA in cancer and genetic research.

Conclusion

ecDNA represents a paradigm shift in understanding cancer biology. By identifying its role in tumour progression and drug resistance, researchers have unveiled a new frontier in oncology. With targeted therapies on the horizon, this breakthrough has the potential to transform cancer treatment and improve patient outcomes.

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