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🧬 Street Smarts: Cancer's Rings of Power

🧬 Street Smarts: Cancer's Rings of Power

Uncovering the hidden DNA circles driving cancer’s growth and resistance

November 11, 2024

Happy Monday!

Welcome to Street Smarts your 5 minute brief on genetic health and business by SeqStreet, the newsletter keeping you frosty with fresh scoops of sequencing news you didn’t know you needed.

In todays issue:

Cancer's Rings of Power
— Uncovering the hidden DNA circles driving cancer’s growth and resistance
Below the Surface: Hidden Role for Mutant RAS
— Newly discovered mechanism for RAS-related cancer progression
Wired to Worry: the New Neurotic Gene Family
— 18 newly discovered neuroticism-linked genes and how they were discovered

FEATURED

Cancer's Rings of Power

Three new studies from Stanford cast a fresh spotlight on extrachromosomal DNA (ecDNA). Once seen as "meh" genetic extras, these rings of circular DNA are actually major players in cancer’s development, spread, and treatment resistance.

First noted in 1965, ecDNA was only recognized as widespread in cancers in 2017. Over the past decade, their importance has become clear: these DNA rings carry oncogenes—cancer promoting genes that drive tumor growth, resistance to immune defenses, and adaptation to drug treatments. The presence of ecDNA rings has also been linked to metastasis and lower patient survival rates.

What’s New:

The trio of research papers published on Nov. 6th in Nature present key insights:

Far more prevalent than previously thought: ecDNA was found in nearly 17% of the 15,000 tumors analyzed.
Mendel’s laws don’t apply here: ecDNA clusters stick together during cell division, letting cancer cells inherit multiple oncogene copies that promote resistance and immune evasion.
An unexpected vulnerability: ecDNAs rely heavily on the checkpoint protein CHK1 due to their intense transcription activity. Blocking CHK1 triggered self-destruction in ecDNA-rich cancer cells—a discovery now being explored in clinical trials with CHK1 inhibitors as a novel treatment for aggressive cancers.

Why it Matters:

These little DNA rings give cancer cells a serious upgrade, helping them grow faster and dodge treatment. But they also expose a weakness: cancer’s dependence on them. By targeting ecDNAs, we might have a new way to strike at cancer’s core—taking their ‘rings of power’ straight to Mordor.

Sequence Deeper

MORE NEWS

Below the Surface: Hidden Role for Mutant RAS

Researchers at the NIH have discovered that RAS genes, big troublemakers in cancer, have a sneaky side. Known for causing chaos on the cell surface, RAS genes also stir up trouble inside the cell nucleus. This new study, published in Nature Cancer, reveals that mutant RAS releases a protein called EZH2, which goes on to break down a helpful tumor-suppressor, DLC1. Blocking RAS can restore DLC1’s cancer-fighting powers.

Why it Matters:

Tests in cancer cells and mice showed that pairing RAS blockers with other cancer drugs is much more effective than using RAS blockers alone. This “power couple” (no…not Blake and Ryan) could be a game-changer, especially for hard-to-treat cancers like pancreatic cancer. Researchers are now exploring ways to turn these findings into new treatment combos that could tackle RAS-driven cancers from multiple angles.

Wired to Worry, The New Neurotic Gene Family

A team in China has mapped out dozens of genes tied to neuroticism by studying both rare and common genetic variants. Neuroticism, a personality trait associated with worry, anxiety, and irritability, often overlaps with neuropsychiatric conditions like depression. The study, published in Nature Human Behaviour, analyzed data from nearly half a million individuals in the UK Biobank, making it the largest exome-wide association study on neuroticism to date. The team identified 56 neuroticism-linked genes, including 18 newcomers to the neuroticism family.

Why it Matters:

Some of these genes appear to be "druggable," hinting at potential targeted therapeutics and personalized treatment for neuropsychiatric disorders. Future plans include scaling up to whole-genome sequencing, aiming for a more complete picture of neuroticism’s family tree. By unraveling these relationships, the study team hopes to pave the way for new, precise treatments that could help manage not only neuroticism but also related conditions like depression.

Thats all for today.

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Until next time, sequence deeply my friends.