Trends in cancer最新文献

Ferroptosis is a variant of regulated cell death (RCD) elicited by an imbalance of cellular redox homeostasis that culminates with extensive lipid peroxidation and rapid plasma membrane breakdown. Since other necrotic forms of RCD, such as necroptosis, are highly immunogenic, ferroptosis inducers have attracted considerable attention as potential tools to selectively kill malignant cells while eliciting therapeutically relevant tumor-targeting immune responses. However, rather than being consistently immunogenic, ferroptosis mediates context-dependent effects on anticancer immunity. The inability of ferroptotic cancer cells to elicit adaptive immune responses may arise from contextual deficiencies in intrinsic aspects of the process, such as adjuvanticity and antigenicity, or from microenvironmental defects imposed by ferroptotic cancer cells themselves or elicited by the induction of ferroptosis in immune cells.

The persistence of drug-sensitive tumors poses a significant challenge in cancer treatment. The concept of bacterial persisters, which are a subpopulation of bacteria that survive lethal antibiotic doses, is frequently used to compare to residual disease in cancer. Here, we explore drug tolerance of cancer cells and bacteria. We highlight the fact that bacteria, in contrast to cancer cells, have been selected for survival at the population level and may therefore possess contingency mechanisms that cancer cells lack. The precise mechanisms of drug-tolerant cancer cells and bacterial persisters are still being investigated. Undoubtedly, by understanding common features as well as differences, we, in the cancer field, can learn from microbiology to find strategies to eradicate persisting cancer cells.

Neutrophils represent the most abundant myeloid cell subtype in the non-small-cell lung cancer (NSCLC) tumor microenvironment (TME). By anti- or protumor polarization, they impact multiple aspects of tumor biology and affect sensitivity to conventional therapies and immunotherapies. Single-cell RNA sequencing (scRNA-seq) analyses have unraveled an extensive neutrophil heterogeneity, helping our understanding of their pleiotropic role. In this review we summarize recent data and models on tumor-associated neutrophil (TAN) biology, focusing on the diversity that evolves in response to tumor-intrinsic cues. We categorize available transcriptomic profiles from different cancer entities into a defined set of neutrophil subclusters with distinct phenotypic properties, to step beyond the traditional binary N1/2 classification. Finally, we discuss potential ways to exploit these neutrophil states in the setting of anticancer therapy.

The cancer mycobiome has recently become a research hotspot. While the intratumor mycobiota is implicated in cancer initiation and progression, the gut mycobiota functions as biomarkers for cancer diagnosis and treatment. In this forum article we highlight the involvement of the mycobiome in correlation-, causation-, and prediction-oriented cancer research and discuss the potential of this burgeoning field.

Immunotherapy shows efficacy for multiple cancer types and potential for expanded use. However, current immune checkpoint inhibitors (ICIs) are ineffective against microsatellite-stable colorectal cancer (CRC), which is more commonly diagnosed. Immunotherapy strategies for non-responsive CRC, including new targets and new combination therapies, are being tested to address this need. Importantly, a subset of inherited germline genetic variants associated with CRC risk are predicted to regulate genes with immune functions, including genes related to existing ICIs, as well as new potential targets in the major histocompatibility complex (MHC) region and immunoregulatory cytokines. We review discoveries in the inherited genetics of CRC related to the immune system and draw connections with ongoing developments and emerging immunotherapy targets.

Ferroptosis, a nonapoptotic form of cell death characterized by iron accumulation and uncontrolled lipid peroxidation, holds promise as a therapeutic approach in cancer treatment, alongside established modalities, such as chemotherapy, immunotherapy, and radiotherapy. However, recent research has raised concerns about its side effects, including damage to immune cells, hematopoietic stem cells, liver, and kidneys, the development of cachexia, and the risk of secondary tumor formation. In this review, we provide an overview of these emerging findings, with a specific emphasis on elucidating the underlying mechanisms, and underscore the critical significance of effectively managing side effects associated with targeted ferroptosis-based therapy.

Gene fusions and rearrangements play a crucial role in tumor biology. They are rare events typically detected in KRAS wild-type (WT) pancreatic tumors. Their identification can inform clinical management by enabling precision oncology, as fusions involving BRAF, FGFR2, RET, NTRK, NRG1, and ALK represent actionable targets in KRAS-WT cancers, and serve diagnostic purposes since fusions involving PRKACA/B represent the diagnostic hallmark of intraductal oncocytic papillary neoplasms (IOPNs). Although they are rare, the therapeutic and diagnostic importance of these genomic events should not be underestimated, highlighting the need for quality-ensured molecular diagnostics in the management of cancer. Herein we review the existing literature on the role of fusion genes in pancreatic tumors and their clinical potential as effective biomarkers and therapeutic targets.

Despite an overall decrease in occurrence, colorectal cancer (CRC) remains the third most common cause of cancer deaths in the USA. Detection of CRC is difficult in high-risk groups, including those with genetic predispositions, with disease traits, or from certain demographics. There is emerging interest in using engineered bacteria to identify early CRC development, monitor changes in the adenoma and CRC microenvironment, and prevent cancer progression. Novel genetic circuits for cancer therapeutics or functions to enhance existing treatment modalities have been tested and verified in vitro and in vivo. Inclusion of biocontainment measures would prepare strains to meet therapeutic standards. Thus, engineered bacteria present an opportunity for detection and treatment of CRC lesions in a highly sensitive and specific manner.