The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
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Rosano, D., Sofyali, E., Dhiman, H. et al. Cancer Discovery. 14 (5): 866–889 (2024).
doi: 10.1158/2159-8290.CD-23-1161.
Summary of the findings
Summary of the findingsLate relapse remains a major clinical challenge in estrogen receptor–positive breast cancer (ER+ BC) patients treated with adjuvant endocrine therapies (ETs). Despite the effectiveness of ETs in delaying relapse by targeting subclinical micrometastases, up to 50% of patients experience relapse through unknown mechanisms likely involving dormancy.
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This study investigated the genetic and transcriptional changes behind tumour awakening by analysing the genomic landscape of late relapse and longitudinally profiling a rare cohort treated with long-term neoadjuvant ET. Complementing these clinical observations, the authors conducted an in vitro evolutionary study in unperturbed settings to record the adaptive strategies of individual cancer lineages along dormancy and awakening.
This study investigated the genetic and transcriptional changes behind tumour awakening by analysing the genomic landscape of late relapse and longitudinally profiling a rare cohort treated with long-term neoadjuvant ET. Complementing these clinical observations, the authors conducted an in vitro evolutionary study in unperturbed settings to record the adaptive strategies of individual cancer lineages along dormancy and awakening.
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The data revealed that ER+ BC cells exposed to ETs enter dormancy in a stochastic pattern through epigenetic reprogramming. Notably, dormant cells can awaken unpredictably, exhibiting divergent phenotypes, and this reactivation doesn’t involve recurrent genetic alterations. Importantly, targeting the epigenome of dormant cells shows promise in combating adaptive resistance to ETs.
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This study highlights the critical role of epigenetic adaptation in the evolution of resistance to ETs and emphasises the potential for developing therapeutic strategies aimed at targeting dormant cancer cells.
This study highlights the critical role of epigenetic adaptation in the evolution of resistance to ETs and emphasises the potential for developing therapeutic strategies aimed at targeting dormant cancer cells.
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Future impact
Through an integrated multi-omic approach, this work enhances the understanding of therapy-induced dormancy. While exposed to endocrine therapies, estrogen receptor-positive breast cancer cells enter dormancy by undergoing extensive heterochromatinization. Targeting the epigenetic changes that underlie dormancy can effectively increase cancer cells’ vulnerability to therapies. This work highlights the importance of developing actionable strategies to target cells entering dormancy. Overall, this study provides novel insights into breast cancer cell adaptive strategies and could inform future therapeutic approaches aimed at improving long-term outcomes for breast cancer patients.
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