Advances in Genome Regulation in Cancer

Dear Colleagues,

The last decade has seen significant advances in our understanding of how the cancer genome is regulated. Following the detailed genetic blueprints arising from the Human Genome Project and consequent Cancer Genome Sequencing Projects, the somatic mutation theory of cancer has become challenged, leading to questions about the rationale for precision oncology [1]. Concurrently, more detailed appreciation of the biological complexity of cancer [2] and cancer-related gene interactions are converging with systems-wide, bioinformatic approaches to better understand the ‘physics of complexity’ [3]. After losing the “war on cancer” we have to recognise that cancer is inherently and secondarily resistant to many treatments and to question why [4]. Recent progress indicates that the human cellular networks have specific “cancer attractors” that evolved during macroevolution and adaptation of cellular organisms to hostile environments [5, 6]. Such, “survival at the brink” of extinction appears enabled by explorative adaptation - competition and oscillations between opposing genome/proteome network states and epigenetic cell fates [7]. Chaotic genome regulation, including via transposons, may help explain cancer aneuploidy and resistance to treatments [8].

Despite this rapid progress, many questions remain. Are there constraints on the degree of chaos? Can cancer progression continue solely as a result of genomic instability, which perpetually increases aneuploidy? Can these processes ensure cancer cell immortality? Do they arrive at some point at the Weismann law of heredity transfer between generations of organisms [7]? Can a cancer cell really undergo reversible soma-to-germ reprogramming and behave like a single organism with a “life-cycle” [9]? Is one of the keys to this conundrum hidden in the germline genes ectopically expressed in cancer and associated with poor survival [10]? Are these same genes involved in ensuring genome order or do they multiply and compound its errors?

Original articles and reviews addressing these essential questions are invited. The potential authors are encouraged to send an Abstract to the Guest-Editor for the preliminary enquiery.

References

1. Brock and Huang 2017; DOI: 10.1158/0008-5472.CAN-17-0448
2. Weinberg 2014; DOI:10.1016/j/cell.2014.03.004
3. Bizzarri et al., 2020; DOI:10.3390/e22080885
4. Amirouchene-Angelozzi et al., 2017; DOI: 10.1158/2159-8290.CD-17-0343
5. Trigos et al., 2018; 10.1038/bjc.2017.398
6. Pienta et al., 2020; DOI: 10.1158/1541-7786.MCR-19-1158
7. Erenpreisa et al., 2020; DOI: 10.1016/j.semcancer.2020.12.009
8. Ye et al., 2021; DOI: 10.3389/fcell.2021.676344
9. Erenpreisa and Cragg 2007; DOI: 10.1016/j.cellbi.2007.08.013
10. Bruggeman et al., 2018; DOI: 10.1038/s41388-018-0357-2

Dr. Jekaterina Erenpreisa
Prof. Dr. Mark Steven Cragg
Prof. Dr. Alessandro Giuliani
Guest Editors

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