Trends in cancer最新文献

Solid tumors generate a local and systemic procoagulant state, placing cancer patients at risk of hemostatic complications. The interplay between the tumor coagulome, a tumor-intrinsic determinant, and surgery-induced coagulopathy may influence the risk of recurrence following complete surgical resection. Perioperative targeting of the coagulome could advance cancer precision treatment.

Precision oncology leverages targetable molecular aberrations to treat cancer. Initially, use of these therapies required biomarker detection in a specific tumor type. Recently, regulatory agencies have approved highly active biomarker-based, tumor-agnostic therapies, which are crucial for the unmet needs of patients with rare cancer, including children with cancer, because an infrequent biomarker in an already rare cancer represents a prohibitive clinical trial accrual barrier. There are also now several 'ag(e)nostic' precision oncology therapies - agnostic to tumor type and also approved for all ages. In this opinion, we provide historical context for the precision oncology field and contend that, moving forward, ag(e)nostic precision oncology approvals should be the norm for this class of therapeutics rather than an exception to the rule.

Cuproptosis is a newly identified form of copper-dependent cell death. Recent studies show that solid tumors evade this process through transcriptional reprogramming, including hypoxia inducible factor 1 subunit alpha (HIF1A) and NFE2 like BZIP transcription factor 2 (NFE2L2) activation and BTB domain and CNC homolog 1 (BACH1) suppression. Targeting these pathways may restore cuproptosis sensitivity, offering a promising strategy to overcome therapy resistance in cancer.

Despite deep and growing knowledge of cytokine functions, immunotherapies based on the control of these molecules have minimally impacted cancer patient management because of limited efficacy and narrow therapeutic windows. Opportunities to enhance efficacy and mitigate side effects arise from local delivery and targeting antitumor cytokines to tumor tissue via chimeric fusion with antibodies (immunocytokines). Conversely, neutralization of protumor cytokines using antibodies, cytokine traps, or receptor antagonists offer the opportunity to increase the efficacy of conventional immunotherapy with checkpoint inhibitors while reducing their side effects. Exploiting the immunobiology of interleukin (IL)-2, IL-12, IL-15, IL-18, and IL-21 in synergistic combinations with other treatments holds promise. The antagonistic neutralization of transforming growth factor-β, tumor necrosis factor, IL-1, IL-6, and CXCR1/2 chemokines and growth differentiation factor 15 also seems to be very convenient, again as part of combination strategies.

The unmet therapeutic need in prostate cancer (PCa), a disease that remains largely incurable after metastasis, underscores the urgency for new treatments. STEAP1 (six transmembrane epithelial antigen of prostate 1) is a cell surface protein highly expressed in >85% prostate tumors but shows little to no presence in normal tissues, making it a promising candidate for targeted therapy. Here, we summarize and discuss recent findings that underscore the promising role of STEAP1 in PCa therapy.

Sublethal apoptotic stress causing the permeabilization of some mitochondria coupled with cytosolic mitochondrial DNA (mtDNA) accumulation is known to promote cellular senescence. Lai et al. have recently demonstrated that this may be accompanied by mtDNA release within extracellular vesicles that promote local immunosuppression via myeloid-derived suppressor cells.

Tumoroids are cultures of patient-derived tumor cells, which are grown in 3D in the presence of an extracellular matrix extract and specific growth factors. Tumoroids can be generated from adult as well as pediatric cancers, including epithelial cancers, sarcomas, and brain cancers. Tumoroids retain multi-omic characteristics of their corresponding tumor and recapitulate interpatient and intratumor heterogeneity. Retrospective and prospective studies have demonstrated that tumoroids predict patient responses to anticancer therapies, making them a promising tool for precision oncology. However, several challenges remain before tumoroids can be fully integrated into clinical decision-making, including success rates of tumoroid establishment and turnaround times. This review discusses the current advances, challenges, and future directions of tumoroid-based models in cancer research and precision therapy.

The incidence of squamous cell carcinoma (SCC) is rising, especially in immunosuppressed individuals, highlighting the need for new prevention strategies. Commensal human papillomaviruses (cHPVs) are associated with cutaneous SCC (cSCC) in immunosuppressed patients. Because of the intricate interactions between T cell immunity and cHPVs in virus-colonized tissues, we propose that enhancing T cell immunity against cHPVs through vaccination could suppress SCC.

The acknowledged relationship between metabolism and cancer retains important potential as a novel target in therapy. Reallocating glucose-lowering drugs (GLDs) in cancer treatment offers valuable perspectives for the ability of these molecules to regulate metabolism at cellular and systemic level. This comprehensive review addresses the therapeutic potential of the main antidiabetic classes of glucose-lowering drugs with emerging anticancer effects, such as metformin, rosiglitazone, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium/glucose cotransporter-2 inhibitors. The multifaceted actions of these drugs are explored, from in vitro evidence to clinical evidence as monotherapy or as a sparing agent with chemotherapy and immunotherapy. For each molecule, unconventional mechanisms, benefits, and limitations are dissected and possible concerns addressed, supporting evidence for the potential use of the drug in cancer.

Cancer cells optimize oncogenic signaling to maintain a defined range for survival. The success of targeted therapeutic inhibitors is based on suppressing signaling below this optimal fitness zone. Conversely, cancers are also susceptible to a clinically underutilized vulnerability - oncogenic hyperactivation. Cytotoxic hyperactivation is observed across diverse cancers, with direct small-molecule activators and inhibitors of negative regulators inducing lethal pathway activation. Deep characterization of the cancer genome and unbiased screening approaches have yielded multiple targets vulnerable to hyperactivation; however, translation into the clinical setting will require defining signaling thresholds, discovering biomarkers, and developing appropriate trial designs. By exploiting cancer's intrinsic vulnerabilities, activation lethality offers a promising therapeutic strategy to expand the treatment landscape and overcome resistance to targeted inhibition.