Hypermutations inside rings of DNA might drive cancer progression

What matters in cancer | 

View this email in your browser Thursday 24 October 2024

Hello Nature readers, This week, we hear about the greatest boost to cervical cancer survival in 25 years, discover a hibernation strategy that could help cancer cells survive starvation and learn that advanced cancers might be driven by rapid mutations in circular DNA.

Ribosomes, the machinery inside cells that make proteins, hibernate by attaching themselves upside down on the surface of mitochondria. (O. Gemin et al./Nature Comm.)

Ribosomes sleep like bats to hibernate Yeast cells survive nutrient shortages by attaching their protein-making ribosomes upside down on the surface of mitochondria — an orientation that causes the ribosomes to shut down and the cell to become dormant. Cancer cells could undergo a similar hibernation to protect themselves during times of nutrient scarcity, say researchers. "Since the adaptive response to nutrient cues is commonly observed in cancer, our study could also provide a molecular understanding of cell persistence in pathological environments," they authors report. The Microbiologist | 4 min read Reference: Nature Communications paper (8 October)

'Biggest gain in survival since 1999' The risk of death from cervical cancer decreased by 40% over five years when women were given chemotherapy followed by chemoradiotherapy instead of chemoradiotherapy alone. Five hundred women randomly received either chemotherapy (carboplatin and paclitaxel) followed by radiotherapy plus cisplatin, or the standard chemoradiation. The five-year survival rate was 80% in the group given the new treatment and 72% in women given the standard treatment. "This is the biggest gain in survival since the adoption of chemoradiation in 1999," said oncologist and co-author Mary McCormack. The Guardian | 4 min read Reference: The Lancet paper (19 October)

In the news Hair loss can be prevented in people undergoing chemotherapy by applying pressure to the scalp instead of cooling it. A helmet-shaped device under development called Lily works by restricting the flow of chemotherapy-containing blood into the hair follicles. Pressure treatment using a portable device is likely to be faster and more comfortable than cooling therapy. (CNN | 6 min read) Five more research articles co-authored by surgical oncologist Sam Yoon have been retracted. Around a dozen articles by the researcher have been pulled since his work came under the scrutiny of scientific sleuth Sholto David. (The New York Times | 6 min read)

Must-read papers

Advanced human cancers have more extrachromosomal DNA than early-stage cancers. (Getty)

Hypermutations in DNA rings drive cancer Rapid mutations in rings of DNA could be causing cancers to become more aggressive. Researchers performed whole-genome sequencing on more than 8,000 tumour samples and found that cancer progression was associated with a higher frequency of hypermutated extrachromosomal DNA. A separate study found that chemotherapy and virus-fighting APOBEC3 enzymes were driving mutations in extrachromosomal DNA in human bladder cancer cells. References: Nature Genetics paper (14 October) & Nature paper (9 October)

A century of cancer-metabolism research Biochemist Otto Warburg first described metabolic changes inside cancer cells in 1923. More than 100 years on, the field is still going strong, as shown in this collection of metabolism articles across Springer Nature journals. One study in the collection reveals an increase in mitochondrial activity as kidney cancer travels to distant organs. Another suggests that the metabolic profile of the primary cancer site influences which tissues the cancer can colonize. Cancer Metabolism 2.0, a Nature Portfolio collection References: Nature paper (14 August) and Nature Metabolism paper (19 August)

Features & opinion

Cancer risk from IUDs a 'statistical illusion'? A Danish study that tracked nearly 80,000 people over two decades has found an association between the use of hormonal intrauterine devices (IUD) and breast cancer. The increased risk is so small in absolute terms that this "might be a statistical illusion rather than a real thing", writes primary care physician Brett Montgomery. For every 10,000 women using a hormonal IUD, there would be 71 more cases of breast cancer over 10-15 years, the study suggests. The risk from IUDs "may be dwarfed by other risks for breast cancer, such as high body weight, physical inactivity, alcohol use, and smoking", Montgomery writes. The Conversation | 5 min read Reference: JAMA research letter (16 October)

42% The percentage of people in the United States who are left with no life savings two years after a cancer diagnosis. (CNBC | 7 min read) Reference: The American Journal of Medicine paper (2018)

Infographic of the week

Tugging, squashing, ripping, moving; these are just some of the mechanical forces at play inside solid tumours that can influence the development and spread of cancer cells. View a larger version of this image here. (Nature Reviews Cancer | 57 min read) (J. A. Linke et al./Nature Rev. Cancer)

Quote of the week "When I was 23 years old, I found out I had cancer… I immediately decided against freezing my eggs." Rachel Hunt wonders whether her "lifelong apathy" towards having biological children prepared her for this moment. (The Washington Post | 4 min read)

This week, I'm mesmerized by the synchronized muscle contractions of two comb jellies that have fused parts of their nervous systems together after being injured. Sea walnuts (Mnemiopsis leidyi) bob around in the ocean on their own most of the time, which could explain why they seem to be unable to distinguish themselves from others of the same species — leading to the fusion. Send synchronized mail, tips and feedback to cancerbriefing@nature.com. Thanks for reading, Felicity Nelson, editor, Nature Briefing: Cancer

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