A broad-spectrum RAS inhibitor for pancreatic cancer

What matters in cancer | 

View this email in your browser Thursday 18 April 2024

Hello Nature readers, This week, we hear that oncologists are no longer flying blind when selecting precision drugs for hard-to-treat child cancers, learn how to prevent exhaustion in cancer-fighting T cells and explore a broad-spectrum RAS inhibitor for pancreatic cancer.

The chance of selecting the right precision drug for a child with relapsed or refractory cancer is so low that "you might as well be pulling numbers out of a hat", says paediatric oncologist Maggie Fader. (FreshSplash/Getty)

Try-everything approach tested in kids Children with difficult-to-treat cancers respond better when precision treatments are selected on the basis of how well they kill the child's cancer cells in a petri dish than when the clinician makes a blind choice. Five out of six children treated using this approach saw their cancers stabilise or shrink. This group had greater progression-free survival and response rates than the eight children given non-guided therapy. "There is no question that patients treated according to drug-sensitivity testing did significantly better than those who didn't," says cancer researcher and oncologist Anthony Letai. "The time is now to investigate this seriously… no cancer patient should depart this Earth due to cancer without one of these tests done." STAT | 12 min read Go into more depth with this Nature feature. Reference: Nature Medicine paper (11 April)

Stem-cell skills prevent CAR T exhaustion Two research groups have independently arrived at the same solution for preventing exhaustion in cancer-fighting T cells: giving them stem-cell powers by boosting their expression of the FOXO1 protein. Researchers found that some CAR T cells performed better in people with leukaemia than others due to higher activation of 41 genes regulated by the master-switch protein FOXO1. CAR T cells that were engineered to have higher FOXO1 activity resembled T memory stem cells, which quickly recognize and attack cancer. Tumours stayed smaller for longer in mice with FOXO1-boosted CAR T cells compared with standard CAR T cells. Nature | 4 min read Reference: Nature paper 1 & 2 (10 April)

In the news Drug shortages in the United States have hit a record high, with 323 drugs in short supply, including 32 chemotherapy agents. (CNN | 3 min read) In a major victory for people living in parts of Louisiana known as 'cancer alley', the US Environmental Protection Agency (EPA) has ruled that manufacturers must limit their emissions of two cancer-causing chemicals: ethylene oxide and chloroprene. "This rule alone will reduce the cancer risk for people living in these communities by 96%," says EPA administrator Michael Regan. (CNN | 3 min read)

Must-read papers

A broad-spectrum drug for pancreatic cancer A drug called RMC-7977 slowed tumour growth and increased survival in mice with pancreatic cancer. RMC-7977 inhibits a broad spectrum of mutated RAS proteins and was well-tolerated in mice, report the authors. RMC-7977 was also potent against a wide range of RAS-mutated cancers in mice, according to a second study by the drug's developer, Revolution Medicines. Reference: Nature paper 1 & paper 2 (8 April)

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Conference highlights

'Full steam ahead' for cancer vaccines The past decade has been a bumpy road for cancer vaccines, but two early-phase clinical trials presented at a recent conference are raising hopes. In a clinical trial of 33 people with head and neck cancer, run by biotechnology company Transgene, none of the people randomized to receive a vaccine after surgery relapsed after 16 months, compared with three in the control group. In another small trial by drug companies BioNTech and Genentech, people with pancreatic cancer were given a vaccine after surgery. Those who developed an immune response were less likely to relapse than those who did not. "I think it's full steam ahead with a bit of caution," says cancer vaccine researcher Catherine Wu. "We've been through deep valleys of despair with vaccines in the past." STAT | 6 min read These abstracts were presented at the American Association for Cancer Research annual meeting in San Diego.

Pancreatic-cancer test with 97% accuracy A blood test has detected early-stage pancreatic cancer with 97% accuracy in an unpublished clinical trial involving 984 people. The 'liquid biopsy' analysed microRNAs trapped inside small vesicles called exosomes in the blood, as well as the levels of the protein CA19-9, which is known to be associated with pancreatic cancer. CNN | 8 min read This abstract was presented at the American Association for Cancer Research annual meeting in San Diego.

Infographic of the week

Tumours are stiffer than healthy tissue because of increased fibrillar collagen deposition in the extracellular matrix. See a larger version of this image here. (Nature Reviews Physics | 38 min read) (Andrew Massey et al/Nature Reviews, Physics)

Quote of the week "I don't think there's a one-size-fits-all time frame, but in general, the sooner the better." Children are "incredibly observant" and they will often notice that something in the environment has changed when a parent is diagnosed with cancer, says social worker Liz Farrell, who works at a breast-cancer clinic. (Scientific American | 6 min read)

This week, I entered The New Yorker's weekly caption contest. Two clowns examine an artwork in a gallery. My caption reads: 'A bit of a caricature, don't you think?' [Cue laughter/judgement.] Research suggests my attempt might have been funnier had I consulted artificial intelligence first. When study participants were prompted by AI-generated concepts of 'appropriate incongruity', they wrote more humorous captions, some of which were "not far behind the winning captions … in terms of funniness," report the authors. Automate your comedy people, and send tips and feedback to cancerbriefing@nature.com. Thanks for reading, Felicity Nelson, editor, Nature Briefing: Cancer

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