Senescence and Tumor Dormancy

Dear Colleagues,

While tumor dormancy and disease recurrence represent primary limitations to the effectiveness of cancer therapy, and are largely responsible for cancer morbidity and mortality, there is limited understanding of the essential nature of tumor dormancy or what factors eventually facilitate escape from this form of stasis. In large part, this is because, by their nature, dormant tumor cells cannot be identified in patients, given that they are often in occult sites such as the bone marrow, are few in number, and lack distinguishing characteristics. Furthermore, when disease recurs, the once dormant cells cannot necessarily be distinguished from tumor cells that never actually entered a dormant state.

Senescence was for years considered a permanent form of growth arrest occurring as a result of telomere shortening, oncogene expression or overexpression and/or tumor cells subjected to chemotherapy or radiation. In recent years, it has become evident that this growth arrest is not, in fact, irreversible, and that subsets of tumor cells that have entered into senescence-mediated growth arrest induced by cancer therapeutics can escape from senescence and regain self-renewal capacity. Consequently, tumor cell senescence and tumor dormancy have fundamental similarities in reflecting a transient state of growth arrest from which the disease can be re-established. This is not to propose that all forms of tumor dormancy and cancer recurrence involve cells induced into and re-emerging from senescence, but only that senescence may reflect some forms of tumor dormancy, and that senescence-associated tumor dormancy may be dependent on the type of malignancy and/or the nature of the senescence-inducing stress.

The recent advent of senolytics, agents that to various extents are effective in eliminating senescent cells, often via the promotion of apoptosis, provides new opportunities for adjuvant cancer treatment. It is therefore possible that the administration of senolytics in combination with chemotherapy and/or radiation might prevent or at least delay disease recurrence from dormancy.

We anticipate that manuscripts submitted for this special issue will address the putative relationship(s) between tumor cell senescence and escape from senescence with tumor dormancy, re-emergence from dormancy and disease recurrence. We would like to emphasize that it is not obligatory that the submissions agree with the premise that senescence and tumor dormancy are closely related, and could argue for alternatives such as, for instance, the involvement of quiescence in tumor dormancy and disease recurrence, the potential contribution of what has been termed “drug-tolerant persister cells”, or address the potential contribution of circulating tumor cells found in the blood of patients with solid tumor malignancies. The identification and analysis of putative models of tumor dormancy and the relationship (or lack thereof) to senescence would also be considered relevant to the thrust of this effort. Controversial perspectives that are supported by sound scientific literature are also encouraged. We look forward to a journal issue that raises the level of discussion and analysis in this highly relevant and timely field.

Prof. Dr. David A. Gewirtz

Guest Editor

Manuscripts should be submitted via our online editorial system at https://imr.propub.com by registering and logging in to this website. Once you are registered, click here to start your submission. Manuscripts can be submitted now or up until the deadline. All papers will go through peer-review process. Accepted papers will be published in the journal (as soon as accepted) and meanwhile listed together on the special issue website. Research articles, reviews as well as short communications are preferred. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office to announce on this website.

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