Trends in cancer最新文献

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.

Tumors subvert T cell metabolism through diverse mechanisms. Ikeda et al. reveal mitochondrial transfer as a tumor-driven immune evasion strategy, where cancer cells deliver dysfunctional mitochondria to T cells, impairing metabolism and inducing exhaustion. These findings highlight mitochondrial dynamics as a promising therapeutic target to improve immunotherapy outcomes.

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.

The molecular and cellular pathways through which breast cancer evades immunosurveillance remain poorly understood. Recent data from Camargo et al. demonstrate that - on recruitment to the tumor microenvironment by ductal macrophages - a heterogeneous population of neutrophils can establish physical contacts with malignant cells within spatial niches that sustain mammary oncogenesis.

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.

Ultra-high dose delivery of radiation (>40 Gy/s), namely FLASH radiation therapy (FLASH-RT), is a novel treatment strategy that maximizes cell kill while sparing normal tissue. Recent data reported by Ni et al. demonstrate that one of the mechanisms through which FLASH-RT promotes inflammation involves the metabolic reprogramming of macrophages to support immune stimulation, thus enhancing immunotherapy in medulloblastoma (MB).

Acetylation is an increasing area of focus for cancer research as it is closely related to a variety of cellular processes through modulation of histone and non-histone proteins. However, broadly targeting acetylation threatens to yield nonselective toxic effects owing to the vital role of acetylation in cellular function. There is thus a pressing need to elucidate and characterize the specific cancer-relevant roles of acetylation for future therapeutic design. Acetylation-mediated protein homeostasis is an example of selective acetylation that affects a myriad of proteins as well as their correlated functions. We review recent examples of acetylation-mediated protein homeostasis that have emerged as key contributors to tumorigenesis, tumor proliferation, metastasis, and/or drug resistance, and we discuss their implications for future exploration of this intriguing phenomenon.

Tertiary lymphoid structures (TLS) are associated with anticancer immunity, but the mechanisms underpinning their formation remain poorly understood. Amisaki et al. have recently shown that IL-33 mediates ILC2 gut-tumoral migration and promotes TLS formation in pancreatic ductal adenocarcinoma (PDAC) by inducing group 2 innate lymphoid cell (ILC2) Ltb expression. This study highlights new potential therapeutic avenues to enhance immunotherapy.

Sensory nerves form a crucial component of the tumor microenvironment (TME) that relays vital information to the central nervous system and modulates tumor progression via immunosurveillance. Afferent activity processed by the brain can sensitize brain circuitry and influence host behaviors. Peripheral sensory signaling (e.g., release of neuropeptides in the TME) can drive phenotypic changes in the tumor immune response, such as increased exhaustion markers and inhibited effector cell activity, which promote cancer progression. In this review we highlight the most recent evidence demonstrating the pivotal role of the sensory nervous system in cancer, with a focus on primary tumor pain, and we discuss the extent to which pain can influence cancer progression and treatment response, including immunotherapeutic strategies.