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).
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Serio, R.N. et al. Cancer Discovery (2024).
doi: 10.1158/2159-8290.CD-23-1332.
Summary and graphical abstract by Alexandra Boitor, EACR Scientific Officer
Summary of the findings
Summary of the findingsThe presence of metastasis to distal tissues is a main indicator of prognosis for cancer patients. Metastatic subclones possess certain characteristics such as increased mobility and the ability to stay dormant over long period of times, which underly their ability to seed distal organs. However metastatic subclones often are not particularly important in the growth of the primary tumour, making it difficult to identify them. Moreover, several reports highlighted the ability of cancer cells to further disseminate from metastatic sites to other organs and back to the primary tumours in a metastatic cascade. Understanding the kinetics of cancer cell dissemination could help develop novel therapeutic strategies targeting mechanisms of metastatic spread.
In this paper, Serio et al. are looking at the patterns of metastatic spread using a mouse model for an aggressive metastatic form of prostate cancer genetically induced through PTEN/TP53 deletion. Using CRISPR/Cas9-based barcoding technology the authors determined the migration histories of cancer cells from several metastatic sites, corresponding to human prostate cancer topologies. The authors observed a high degree of clonal heterogeneity from the primary tumour in the metastatic seeding, however, only a few clones showed the ability to invade. Most metastasis observed originated from the primary tumour, with secondary seeding being an even more infrequent event, and re-seeding of the primary tumour being an exceptional occurrence. The authors observed a widespread distribution of the initiator clones between metastatic sites suggesting polyclonal metastatic seeding might occur early in tumorigenesis. The mutations driving tumour formation are likely to impact the adaptations that cells undergo during the metastatic process hence altering the trajectories of metastatic spread. Therefore, future work should focus on investigating different starting gene combinations.
