Trends in cancer最新文献

The classical view of cancer as a genetically driven disease has been challenged by recent findings of oncogenic mutations in phenotypically healthy tissues, refocusing attention on non-genetic mechanisms of tumor initiation. In this context, gene-environment interactions take the stage, with recent studies showing how they unleash and redirect cellular and tissue plasticity towards protumorigenic states in response to the exposome, the ensemble of environmental factors impinging on tissue homeostasis. We conceptualize tumor-initiating plasticity as a phenotype-transforming force acting at three levels: cell-intrinsic, focusing on mutant epithelial cells' responses to environmental variation; reprogramming of non-neoplastic cells of the host, leading to protumor micro- and macroenvironments; and microbiome ecosystem dynamics. This perspective highlights cell, tissue, and organismal plasticity mechanisms underlying tumor initiation that are shaped by the exposome, and how their functional investigation may provide new opportunities to prevent, detect, and intercept cancer-promoting plasticity.

Immunotherapy has transformed cancer treatment paradigms, but its effectiveness depends largely on the immunogenicity of the tumor. Unfortunately, the high resemblance of cancer to normal tissues makes most tumors immunologically 'cold', with a poor response to immunotherapy. Danger signals are critical for breaking immune tolerance and mobilizing robust, long-lasting antitumor immunity. Recent studies have identified inflammatory cell death modalities and their power in providing danger signals to trigger optimal tumor suppression. However, key mediators of inflammatory cell death are preferentially silenced during early tumor immunoediting. Strategies to rejuvenate inflammatory cell death hold great promise for broadening immunotherapy-responsive tumors. In this review, we examine how inflammatory cell death enhances tumor immunogenicity, how it is suppressed during immunoediting, and the potential of harnessing it for improved immunotherapy.

Despite a decline in global incidence, gastric cancer (GC) remains a major health concern. The development of GC is a sequential, multistage maladaptive process involving numerous different factors. Understanding the complexity of GC development is crucial for early detection, effective treatment, and, ultimately, prevention. In this respect, identifying the impact of risk factors contributing to the emergence or progression of GC, such as Helicobacter pylori infection, host and bacterial genetics, alcohol consumption, smoking, and preserved foods, will aid in combatting this disease. In this review, we focus on recent developments in understanding the role of the microbiome, dysfunctional molecular pathways, and immune evasion in gastric pathophysiology. We also highlight challenges and advances in treatment of GC.

The molecular mechanisms of switch/sucrose nonfermentable (SWI/SNF)-related BAF chromatin remodeling complex subunit ATPase 2 (SMARCA2) degradation remain elusive. Recently, Kotagiri et al. revealed that SMARCA2 degradation induces enhancer reprogramming in SMARCA4-mutant lung cancer cells, rendering enhancers of key cell-cycle genes inaccessible and suppressing their expression. In addition, the authors identified that transcriptional enhanced associate domain (TEAD) inhibitors synergize with SMARCA2 degraders in inhibiting SMARCA4-mutant lung cancer growth.

Obesity is a condition of excess body fat. Although it has been identified as a risk factor for multiple cancers in part because of its 'metainflammatory' state, it has also been paradoxically associated with improved response to immune checkpoint inhibition. To study obesity, one must first understand how best to define it. In this opinion article, we briefly discuss factors that are impacting net effects of obesity and highlight complementary measures that should be considered beyond body mass index (BMI) when attempting to assess the potential effects of obesity in cancer.

Pathogenic variants of isocitrate dehydrogenase 1 and 2 (IDH1/2) genes are present in approximately 20% of acute myeloid leukemia (AML) cases, resulting in the oncometabolite R-2-hydroxyglutarate (R-2-HG). The accumulation of R-2-HG in leukemic cells and in their niche induces epigenetic modifications, profound rewiring of the cellular metabolism, and microenvironmental remodeling. These changes promote cellular differentiation bias, enhancing the survival and proliferation of leukemic cells, and thus playing a pivotal role in leukemogenesis and resistance to standard AML therapy. This review focuses on the different perspectives offered by studying metabolism and resistance to standard treatments in AML with IDH1 or IDH2 pathogenic variants, for the development of new biomarkers and therapeutic solutions.

The phosphoinositide 3-kinases (PI3Ks) have been the focus of a significant body of cancer research since their discovery nearly 40 years ago. These lipid kinases are now known to play central roles in cancer cell proliferation, survival, migration, metabolism, and immunity and serve as the target of numerous investigational and approved therapeutics. One of these kinases, the unique class IB PI3Kγ, which is highly expressed in myeloid lineage cells and myeloid leukemias, plays prominent roles in tumor immune suppression. Inhibition of this kinase has promoted improved antitumor immune responses in recent solid tumor preclinical studies and clinical trials. New studies also identify this kinase as a driver of acute myeloid leukemia self-renewal and as a new target for the treatment of aggressive leukemias.

Temozolomide (TMZ), the standard first-line chemotherapy for glioblastoma multiforme (GBM), has been a cornerstone of treatment despite its known limitations. We propose critically assessing TMZ's potential to induce multiple regulated cell death modalities and leveraging their immunogenic properties to develop novel strategies for overcoming the resistance of GBM and enhancing its therapy.

Multiple strategies have been clinically employed as combination partners to enhance the therapeutic efficacy of immune checkpoint inhibitors (ICIs). Although these combinations have demonstrated improved effectiveness in some instances, each presents its own limitations. Autophagy-targeting therapy offers several advantages when combined with ICIs, including enhanced tumor immunogenicity, reduced side effects, and broader applicability to diverse patient populations. However, emerging evidence reveals complex reciprocal regulation between autophagy and immune checkpoints which may complicate combination treatments targeting these two systems. This review focuses on the reciprocal interplay between autophagy and immune checkpoints, and provides valuable guidelines for the determination and adjustment of therapeutic regimens in the future.

The tumor microenvironment (TME) is a complex, highly structured, and dynamic ecosystem that plays a pivotal role in the progression of both primary and metastatic tumors. Precise assessment of the dynamic spatiotemporal features of the TME is crucial for understanding cancer evolution and designing effective therapeutic strategies. Cancer is increasingly recognized as a systemic disease, influenced not only by the TME, but also by a multitude of systemic factors, including whole-body metabolism, gut microbiome, endocrine signaling, and circadian rhythm. In this review, we summarize the intrinsic, extrinsic, and systemic factors contributing to the formation of 'cold' tumors within the framework of the cancer-immunity cycle. Correspondingly, we discuss potential strategies for converting 'cold' tumors into 'hot' ones to enhance therapeutic efficacy.