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N6-Methyladenosine (m6A) is the most abundant, dynamic, and reversible epigenetic RNA modification that is found in coding and non-coding RNAs. Emerging studies have shown that m6A and its regulators affect multiple steps in RNA metabolism and play broad roles in various cancers. Worldwide, breast cancer is the most prevalent cancer in female. It is a very heterogeneous disease characterized by genetic and epigenetic variations in tumor cells. Increasing evidence has shown that the dysregulation of m6A-related effectors, as methyltransferases, demethylases, and m6A binding proteins, is pivotal in breast cancer pathogenesis. In this review, we have summarized the most up-to-date research on the biological functions of m6A modification in breast cancer and have discussed the potential clinical applications and future directions of m6A modification as a biomarker as well as a therapeutic target of breast cancer. [ABSTRACT FROM AUTHOR]

Platforms competition affects both the structure of the whole industry and the fate of the individual companies within it. The extant studies either simply divide the participants of a platforms war into suppliers and consumers or adopt unbounded rationality assumptions. This paper constructs a game model that includes platforms, suppliers, and the final consumers. We analyze the condition and stability of each equilibrium and the impacts of the characteristics of the core and complementary products on the equilibrium by using the method of evolutionary game. Our results show the following: (1) If the two platforms initially have separate advantages in terms of the number of suppliers or consumers, there will be an equilibrium of the coexistence; otherwise, there will be an equilibrium of single platform dominating. (2) The equilibrium of a single platform dominating is more stable than that of the coexistence of multiple platforms. (3) Incidental shocks to the number of suppliers are more likely to break the coexistence equilibrium than consumers. (4) Platforms with poor core product quality and a high price for core and complementary products can coexist with other superior platforms only if the former has more consumers and suppliers at the beginning of the competition. [ABSTRACT FROM AUTHOR]

Despite recent advances in immunotherapy with immune checkpoint inhibitors (ICI), many patients with non-small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. In situ vaccination (ISV) with engineered viruses has emerged as a promising antigen-agnostic strategy that can both condition the tumor microenvironment (TME) and augment anti-tumor T cell responses to overcome immune resistance. We engineered a live attenuated viral vaccine, Hyper-Interferon Sensitive virus (HIS), by conducting a genome-wide functional screening and introducing eight interferon (IFN)-sensitive mutations in the influenza genome. Compared to wild-type (WT) influenza, HIS replication was attenuated in immunocompetent hosts, enhancing its potential as a safe option for cancer therapy. HIS ISV elicited robust yet transient type I IFN responses in murine NSCLCs, leading to an enrichment of polyfunctional effector Th1 CD4 and cytotoxic CD8 T cells into the tumor. HIS ISV demonstrated enhanced anti-tumor efficacy compared to WT in multiple syngeneic murine models of NSCLC with distinct driver mutations and varying mutational burden. This efficacy was dependent on host type 1 IFN responses and T lymphocytes. HIS ISV overcame resistance to anti-PD-1 in LKB-1 deficient murine NSCLC, resulting in improved overall survival and enduring systemic tumor-specific immunity. These studies provide compelling evidence to support further clinical evaluation of HIS as a novel 'off-the-shelf' ISV strategy for patients with NSCLC refractory to ICI.