Why in news
Recent studies published in Nature have highlighted the pivotal role of extrachromosomal DNA (ecDNA) in cancer progression and drug resistance.
The research challenges traditional genetics by showing that ecDNA is passed on in clusters during cell division, which could give cancer cells an advantage.
What is ecDNA?
ecDNA stands for extrachromosomal DNA, a small fragment of DNA that floats freely inside the nucleus.
It forms when part of the DNA breaks away from chromosomes due to processes like chromothripsis (DNA breakage) or copying errors
This DNA is not fixed to the chromosome, and can interact with other ecDNA fragments, often containing oncogenes (mutated genes that cause cancer).
ecDNA’s Role in Cancer Growth
Oncogenes on ecDNA are more active than those on chromosomes, leading to accelerated tumour growth.
ecDNA forms hubs where oncogenes are expressed more intensely, contributing to cancer's evolution and drug resistance.
It can result in up to 4x more expression of certain oncogenes compared to chromosomal DNA, helping tumours grow faster.
Violation of Mendel's Law
Traditionally, genes on the same chromosome are inherited together (Mendel’s third law of independent assortment).
ecDNA clusters during cell division and is passed on in groups to daughter cells, a phenomenon known as the “jackpot effect”.
This challenges genetic inheritance principles, giving cancer cells an advantage by preserving favorable genetic traits over multiple generations.
Potential Vulnerabilities in ecDNA-driven Cancers
The abnormal behavior of ecDNA causes a conflict with the cell’s machinery that can lead to DNA damage.
Cancer cells with ecDNA rely heavily on a protein called CHK1 to fix DNA and continue growing.
Researchers discovered that blocking CHK1 with a drug (BBI-2779) kills cancer cells with ecDNA, offering a potential new treatment approach.
COMMENTS