The 2019 coronavirus disease (COVID-19) pandemic caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created an unprecedented global crisis for the infrastructure sectors, including economic, political, healthcare, education, and research systems. Although over 90% of infected individuals are asymptomatic or manifest noncritical symptoms and will recover from the infection, those individuals presenting with critical symptoms are in urgent need of effective treatment options. Emerging data related to mechanism of severity and potential therapies for patients presenting with severe symptoms are scattered and therefore require a comprehensive analysis to focus research on developing effective therapeutics. A critical literature review suggests that the severity of SARS-CoV-2 infection is associated with dysregulation of inflammatory immune responses, which in turn inhibits the development of protective immunity to the infection. Therefore, the use of therapeutics that modulate inflammation without compromising the adaptive immune response could be the most effective therapeutic strategy.

Species evolve by mutations and epigenetic changes acting on individuals in a population; tumors evolve by similar mechanisms at a cellular level in a tissue. This article reviews growing evidence about tumor dormancy and suggests that (i) cellular malignancy is a natural byproduct of evolutionary mechanisms, such as gene mutations and epigenetic modifications, which is manifested in the form of tumor dormancy in healthy individuals as well as in cancer survivors; (ii) cancer metastasis could be an early dissemination event that could occur during malignant dormancy even before primary cancer is clinically detectable; and (iii) chronic inflammation is a key factor in awakening dormant malignant cells at the primary site, leading to primary cancer development, and at distant sites, leading to advanced stage diseases. On the basis of this evidence, it is reasonable to propose that we are all cancer survivors rather than cancer-free individuals because of harboring dormant malignant cells in our organs. A better understanding of local and metastatic tumor dormancy could lead to novel cancer therapeutics for the prevention of cancer. Cancer Res; 77(10); 2564–9. ©2017 AACR.

Tumor dormancy, a clinically undetectable state of cancer, makes a major contribution to the development of multidrug resistance (MDR), minimum residual disease (MRD), tumor outgrowth, cancer relapse, and metastasis. Despite its high incidence, the whole picture of dormancy-regulated molecular programs is far from clear. That is, it is unknown when and which dormant cells will resume proliferation causing late relapse, and which will remain asymptomatic and harmless to their hosts. Thus, identification of dormancy-related culprits and understanding their roles can help predict cancer prognosis and may increase the probability of timely therapeutic intervention for the desired outcome. Here, we provide a comprehensive review of the dormancy-dictated molecular mechanisms, including angiogenic switch, immune escape, cancer stem cells, extracellular matrix (ECM) remodeling, metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced p38 signaling pathways. Further, we analyze the possibility of leveraging these dormancy-related molecular cues to outmaneuver cancer and discuss the implications of such approaches in cancer treatment.

Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy