Mutant p53 drives anti-oestrogen therapy resistance in ovarian cancer


Why do hormone-blocking drugs sometimes fail in ovarian cancer? Scientists at The Wistar Institute have uncovered a key reason. Their study [1] shows that mutant p53, a protein altered in 96% of high-grade serous ovarian cancers, disrupts oestrogen signalling, leaving tumours resistant to hormone-blocking therapy and pointing to potential strategies to restore treatment effectiveness.


Importantly, the team found a way to override this resistance using a drug already in clinical trials. By combining the treatment with anti-oestrogen therapy, previously resistant tumours regained sensitivity — offering a potential new lifeline for patients.


“Mutant p53 has been a major roadblock in hormone therapy,” said Maureen Murphy, PhD, Deputy Director of the Ellen and Ronald Caplan Cancer Center and senior author of the study. “Now we know why treatments fail, and we have a strategy to make them work.”


High-grade serous ovarian cancer remains a deadly disease, with an 80% relapse rate after chemotherapy. Although most tumours


express oestrogen receptors, anti-oestrogen drugs show limited clinical benefi t. Murphy’s team traced the problem to mutant p53 physically binding oestrogen receptors, disrupting crucial hormone signalling.


“This combination therapy could move into clinical trials relatively quickly,” Murphy added. “And the fi ndings may extend beyond ovarian cancer, potentially explaining hormone therapy resistance in other cancers like breast cancer.”


Collaborating with the Helen F. Graham Cancer Center & Research Institute and the University of Pennsylvania, the researchers confi rmed that silencing mutant p53 restores drug sensitivity. They also tested rezatapopt, a compound that refolds a specifi c p53 variant, and found it dramatically boosted response to hormone therapy.


The team is now expanding their work to other p53 variants and developing methods to identify which patients could benefi t most from p53-targeted combination treatments. Work supported by: National Institutes of Health (NIH) grants CA102184 and CA266075


(M.E.M.); Department of Defense grant HT94252410206 (N.Z.); V Foundation for Cancer Research grant V2024-026 (N.Z.); and the Elaine M. Ominsky, Ph.D. Breast Cancer Research Endowed Fund (M.E.M.).


More information online: ilmt.co/PL/b8lZ


1. Mutant p53 Binds and Controls Estrogen Receptor Activity to Drive Endocrine Resistance in Ovarian Cancer published in Genes and Development, 2025. Online publication.


66194pr@reply-direct.com Meteorite crater microbes produce methane — a hint at life on Mars


Working inside the Siljan impact structure, researchers recovered fl uids from 400 metres below ground and discovered an active microbial community capable of generating methane. The team enriched the samples in the lab and found that the microbes readily produced methane from several carbon sources, including naturally occurring oil trapped within the crater’s ancient rocks.


Genomic and transcriptomic sequencing revealed an unusual two-member partnership: Acetobacterium sp. KB-1 and Candidatus Methanogranum gryphiswaldense.


Together they run a single metabolic pathway - methyl-reduction - leaving behind an exceptionally heavy carbon-isotope signature, with δ¹³C values reaching 98.6‰.


This chemical fi ngerprint provides a clear marker of life-driven methane formation in the deep subsurface.


“Impact craters are not just geological scars - they can be microbial havens,” said lead author Femke van Dam, Linnaeus University, Sweden. “Our fi ndings suggest that similar environments on Mars could host life, especially given the methane detected in the Martian atmosphere near impact craters.”


Senior author Henrik Drake added: “The Siljan crater offers a window into life’s resilience. If microbes can thrive here, they might also persist in impact structures on other planets.”


The discovery highlights the role impact craters may play as long-term refuges for life - on Earth and potentially on other planets


Credit: Linnaeus University


Researchers analysed subsurface fl uid samples from the Siljan impact crater in Sweden. Credit: Linnaeus University


A fractured meteorite crater in central Sweden has turned out to be a thriving home for methane-producing microbes. This fi nding gives scientists a rare glimpse into Earth’s deep biosphere and strengthens the case for life in similar environments on Mars [1].


- and offers a new framework for interpreting methane signals in planetary exploration.


More information online: ilmt.co/PL/OmR1


1. Active methylotrophic methanogenesis by a microbial consortium enriched from a terrestrial meteorite impact crater published in mBio.


Methane naturally escaping from fractures in the Siljan impact crater.. Credit: Linnaeus University 66284pr@reply-direct.com


Rewiring fruit fly brains wins 2025 Eppendorf & Science Prize


Cheng Lyu, a postdoctoral fellow at Stanford University, has been awarded the 2025 Eppendorf & Science Prize for Neurobiology for his innovative work on rewiring the olfactory neural circuit in fruit fl ies.


His research sheds light on the molecular mechanisms that guide olfactory receptor neurons in choosing a single synaptic partner from numerous possibilities, offering new insights into the fundamental principles of neural circuit assembly.


Lyu’s experiments revealed that the fl y’s olfactory network develops its three- dimensional structure through a series of one- dimensional steps. By carefully manipulating this process, he was able to rewire the neural


Cheng Lyu.


circuit and even modify the fl ies’ courtship behaviour, linking genetic variation through circuit assembly to observable behavioural outcomes.


The prize also recognises two fi nalists for their outstanding contributions to neurobiology. Constanze Depp from the Broad Institute of MIT and Harvard explored the role of myelin and oligodendrocytes in Alzheimer’s disease, while Sara Mederos of the Sainsbury Wellcome Centre investigated how the brain adapts fear responses and learns to suppress them.


The Eppendorf & Science Prize, awarded annually since 2002, celebrates early-career scientists under 35 who make exceptional


contributions through hands-on laboratory research. Winners receive USD 25,000, full support to attend the prize ceremony at the Society for Neuroscience meeting, and the opportunity to publish an essay about their research in Science.


Finalists also have their essays published and receive full support to attend the ceremony.


The prize was presented on 16th November 2025 in San Diego, and applications for the next cycle are due on 15th June 2026.


More information online: ilmt.co/PL/ZO3N 66139pr@reply-direct.com


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