Trends in Cancer

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...

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...

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...

Chimeric antigen receptor (CAR) T cell therapy is a medical breakthrough in the treatment of B cell malignancies. There is intensive focus on developing solid tumor-targeted CAR-T cell therapies. Although clinically approved CAR-T cell therapies target B cell lineage antigens, solid tumor targets include neoantigens and tumor-associated antigens (TAAs) with diverse roles in tumor biology. Multiple early-stage clinical trials now report encouraging signs of efficacy for CAR-T cell therapies that target solid tumors...

Cancer metastasis causes over 90% of cancer patient fatalities. Poor prognosis is determined by tumor type, the tumor microenvironment (TME), organ-specific biology, and animal physiology. While model organisms do not fully mimic the complexity of humans, many processes can be studied efficiently owing to the ease of genetic, developmental, and cell biology studies. For decades, Drosophila has been instrumental in identifying basic mechanisms controlling tumor growth and metastasis. The ability to generate clonal populations of distinct genotypes in otherwise wild-type animals makes Drosophila a powerful system to study tumor-host interactions at the local and global scales...

Prostate cancer (PC) is immunosuppressive and refractory to immunotherapy. Infiltration of myeloid-derived suppressor cells (MDSCs) and senescent-like neutrophils and T cell exhaustion are observed in the tumor microenvironment (TME) following androgen receptor (AR) antagonism with antiandrogens or androgen ablation. De novo post-translational acetylation of the AR, HOXB13, and H2A at K609, K13, and K130, respectively, and phosphorylation of H4 at Y88 have emerged as key epigenetic modifications associated with castration-resistant PC (CRPC)...

In a recent study in Cancer Cell, Sreekumar et al. used therapy-associated breast cancer mouse models as well as in vitro dormancy models to identify extracellular matrix (ECM)-related tumor cell-autonomous mechanisms of dormancy in residual tumor cells (RTCs). The study reveals an important role of the glycosylation of proteoglycans in sustaining dormancy and opens the door to leverage this biology to eliminate RTCs and prevent recurrence.

Cancer remains a leading cause of morbidity and mortality, and a paradigm shift is needed to fundamentally revisit drug development efforts. Pigs share close similarities to humans and may serve as an alternative model. Recently, a transgenic 'Oncopig' line has been generated to induce solid tumors with organ specificity, opening the potential of Oncopigs as a platform for developing novel therapeutic regimens.

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...

Accumulating studies have demonstrated the presence of viable and metabolically active bacterial communities within a range of solid tumor types. However, the precise mechanisms by which these microbes modulate their infected tumor niches or impact patient responses to cancer treatments remain to be elucidated. Recently, Colbert et al. revealed that L-lactate produced by intratumoral Lactobacillus iners reprograms metabolic capabilities of cervical tumors to support chemoradiotherapy resistance. This finding has implications for many solid cancer types...

Identifying tumor-specific antigenic peptides beyond mutational events is essential for developing effective antitumor immunotherapies. In a recent study, Huang et al. identified an immunogenic cryptic peptide encoded by the circular RNA circFAM53B, through integrating mass spectrometry and ribosome sequencing data from breast cancer samples, and demonstrated its antitumor immunogenicity.

In a recent study, Kerzel et al. report a novel therapeutic strategy to engineer tumor-associated macrophages (TAMs) in vivo by inducing the expression of IFNα in these cells. This approach enables improved antigen presentation and T cell activation, leading to controlled tumor growth in multiple murine models of liver metastasis.

Mammalian cells react to the accumulation of double-stranded (ds)DNA in the cytosol by secreting antiviral and proinflammatory cytokines, notably type I interferon (IFN). Recent data reported by Tani et al. demonstrate that overactivation of this pathway is prevented by an adaptive feedback mechanism elicited by type I IFN receptors and executed by the exonuclease three prime repair exonuclease 1 (TREX1).

The tumor microenvironment (TME) is an integral part of tumors and plays a central role in all stages of carcinogenesis and progression. Each organ has a unique and heterogeneous microenvironment, which affects the ability of disseminated cells to grow in the new and sometimes hostile metastatic niche. Resident stromal cells, such as fibroblasts, osteoblasts, and astrocytes, are essential culprits in the modulation of metastatic progression: they transition from being sentinels of tissue integrity to being dysfunctional perpetrators that support metastatic outgrowth...

About 20% of breast and gastric cancers and 3% of colorectal carcinomas overexpress the human epidermal growth factor receptor 2 (HER2) and are sensitive to HER2-directed agents. The expression of HER2 may differ within the same tumoral lesion (spatial intralesional heterogeneity), from different tumor locations (spatial interlesional heterogeneity), and throughout treatments (temporal heterogeneity). Spatial and temporal heterogeneity may impact on response and resistance to HER2-targeting agents and its prevalence and predictive role changes across HER2-overexpressing solid tumors...

The field of oncology has witnessed an extraordinary surge in the application of big data and artificial intelligence (AI). AI development has made multiscale and multimodal data fusion and analysis possible. A new era of extracting information from complex big data is rapidly evolving. However, challenges related to efficient data curation, in-depth analysis, and utilization remain. We provide a comprehensive overview of the current state of the art in big data and computational analysis, highlighting key applications, challenges, and future opportunities in cancer research...

Clinical academics can effectively advocate for cultural and policy transformations to improve health outcomes; but where do you begin? We present a case study of academics from Melanoma Institute Australia (MIA) who are engaging with the public, media, and policymakers to affect meaningful change in melanoma skin cancer.

Novel tissue-agnostic therapeutics targeting driver mutations in tumor cells have been recently approved by FDA, driven by basket trials that have demonstrated their efficacy and safety across diverse tumor histology. However, the relative rarity of primary brain tumors (PBTs) has limited their representation in early trials of tissue-agnostic medications. Thus, consensus continues to evolve regarding utility of tissue-agnostic medications in routine practice for PBTs, a diverse group of neoplasms characterized by limited treatment options and unfavorable prognoses...

Acute leukemia is characterized by clonal heterogeneity that contributes to poor drug responses in patients. Despite treatment advances, the occurrence of relapse remains a major barrier to achieving cures as current therapeutic approaches are inadequate to effectively prevent or overcome resistance. Given that only a few genetic mutations are associated with relapse in acute leukemia patients, there is a growing focus on 'non-genetic' mechanisms that affect the hallmarks of cancer to allow leukemic cells to survive post therapy...

Multidisciplinary patient-centered networks offer access to difficult-to-get samples and initiate projects from human material. Improving such networks to include 'living' samples could be transformative, not only for research but for clinical trial design, especially when focused on unmet clinical needs, such as brain metastasis.