No abstract

Cancer cell dormancy is a common feature of human tumors and represents a major clinical barrier to the long-term efficacy of anticancer therapies. Dormant cancer cells, either in primary tumors or disseminated in secondary organs, may reawaken and relapse into a more aggressive disease. The mechanisms underpinning dormancy entry and exit strongly resemble those governing cancer cell stemness and include intrinsic and contextual cues. Cellular and molecular components of the tumor microenvironment persistently interact with cancer cells. This dialog is highly dynamic, as it evolves over time and space, strongly cooperates with intrinsic cell nets, and governs cancer cell features (like quiescence and stemness) and fate (survival and outgrowth). Therefore, there is a need for deeper insight into the biology of dormant cancer (stem) cells and the mechanisms regulating the equilibrium quiescence-versus-proliferation are vital in our pursuit of new therapeutic opportunities to prevent cancer from recurring. Here, we review and discuss microenvironmental regulations of cancer dormancy and its parallels with cancer stemness, and offer insights into the therapeutic strategies adopted to prevent a lethal recurrence, by either eradicating resident dormant cancer (stem) cells or maintaining them in a dormant state.

Background and Objective: Hot and cold temperatures significantly increase the risk of death in many regions of the world. Different measures of temperature, including minimum, maximum and apparent temperature, have been used in previous research. Which temperature measure is the best predictor of mortality is not known. Methods: We used mortality data from 106 cities in the US NMMAPS study (years 1987-2000). We examined the association between temperature and mortality using Poisson regression and fitted a non-linear spline for temperature. We examined five measures of temperature, the effect of including relative humidity, and various degrees of freedom for the temperature spline. The best model was defined as that with the minimum absolute residual. The residuals were calculated using crossvalidation. Results: Maximum temperature was selected as the best temperature measure the most often (40 cities in the Ն65-year age group), and apparent temperature the least often (8 cities in the Ͻ65-year age group). Maximum temperature was the best measure in 10 out of 12 months in both age groups. Geographically, maximum temperature was the best measure in cold regions, and minimum temperature in warm regions. Humidity was important in almost every city in the Ն65 year age group. The seasonal variation in humidity showed a surprising peak in usefulness in winter. Conclusion: Apparent temperature is no better than standard measures of temperature in predicting mortality. Maximum temperature was generally the best measure in cold climates and minimum temperature in warm climates. Humidity is an important predictor of mortality in the elderly and its effect should be estimated separately from temperature.

Cancer stem cells (CSCs) are a subpopulation of cancer cells endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms of acquired resistance are increasingly being discovered, but molecular insights into the evolutionary process of CSCs are limited. Here, we show that type I interferons (IFNs-I) function as molecular hubs of resistance during immunogenic chemotherapy, triggering the epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring of cancer cells towards stemness and immune escape. Accordingly, KDM1B inhibition prevents the appearance of IFN-I-induced CSCs, both in vitro and in vivo. Notably, IFN-I-induced CSCs are heterogeneous in terms of multidrug resistance, plasticity, invasiveness and immunogenicity. Moreover, in breast cancer (BC) patients receiving anthracycline-based chemotherapy, KDM1B positively correlated with CSC signatures. Our study identifies an IFN-I → KDM1B axis as a potent engine of cancer cell reprogramming, supporting KDM1B targeting as an attractive adjunctive to immunogenic drugs to prevent CSC expansion and increase the long-term benefit of therapy.