Trends in cancer最新文献

Clinically approved treatments for advanced liver cancer often lack potency because of the heterogeneous characteristics of hepatocellular carcinoma (HCC). This complexity is largely driven by context-dependent inflammatory responses brought on by diverse etiologies, such as metabolic dysfunction-associated steatohepatitis (MASH), the genetic makeup of cancer cells, and the versatile adaptability of immune cells, such as myeloid cells. In this review, we discuss the evolutionary dynamics of the immune landscape, particularly that of liver-resident Kupffer cells (KCs), TREM2⁺, and SPP1⁺ macrophages with an active role during liver disease progression, which eventually fuels hepatocarcinogenesis. We highlight exploitable immunomodulatory avenues amenable to mitigate both the inherent pathological characteristics of liver cancers and the associated external factors that favor malignancy, paving a roadmap toward improving the management and therapeutic outcome for patients with HCC.

Despite significant milestones in cancer immunotherapy, tumor cells often escape immune surveillance. Zhou et al. revealed that the pivotal ferroptosis suppressor glutathione peroxidase 4 (GPX4) can undergo palmitoylation by zDHHC8, enhancing ferroptosis resistance. This study highlights the potential of targeting GPX4 palmitoylation to enhance cytotoxic T cell-mediated ferroptosis of tumor cells.

The TP53 p.R337H variant, prevalent in Southern Brazil, is linked to variable cancer risk for pediatric and adult cancers. Unlike high-penetrance TP53 pathogenic variants, many carriers remain cancer free. Genetic modifiers influence risk, supporting a 'probabilistic' model. Ongoing studies aim to refine risk stratification, improve surveillance, and advance precision medicine for hereditary cancer.

The global incidence of endometrial cancer is on the rise, marked by a notable surge in early-onset endometrial cancer (EOEC; age at diagnosis <50 years). By contrast to late-onset cases, EOEC displays distinct clinical, pathological, and molecular characteristics. The enhanced understanding of the disease's pathophysiology, enabling a more precise differentiation between low-risk and high-risk patients, could facilitate the establishment of risk-stratified treatments that preserve ovarian function and fertility in low-risk EOEC cases. In this review, we delve into the distinctive epidemiological, molecular, and clinical characteristics of EOEC, as well as early noninvasive screening and fertility preservation treatments.

The tumor microenvironment (TME) comprises heterogeneous cell types that closely interact with each other. Crosstalk among the TME components determines antitumor immune responses and their sensitivity to therapies such as immunotherapy. Recent studies published in Cancer Cell by Tang et al. and Zhu et al. identify two novel metabolic adaptations that tumors use to facilitate immune evasion. These targetable mechanisms suggest new avenues to improve antitumor immune responses.

Unconventional T cells, such as invariant natural killer T (iNKT), γδ T, and mucosal-associated invariant T (MAIT) cells, play a pivotal role in bridging innate and adaptive immunity. Their capacity for rapid tumor targeting and effective modulation of the tumor microenvironment (TME) makes them promising candidates for cancer immunotherapy. Advances in chimeric antigen receptor (CAR) engineering have further highlighted their therapeutic potential, particularly for treating challenging cancers. Notably, these cells exhibit favorable safety profiles, enhancing their viability as off-the-shelf therapeutic options. We provide a comprehensive analysis of the clinical applications of CAR-engineered unconventional T cells, focusing on genetic modifications, manufacturing processes, preconditioning regimens, and dosing strategies. We discuss successful examples from recent clinical trials and explore future directions for utilizing these cells in cancer therapy and beyond.

The complex network of proteins that regulate chromatin and DNA methylation landscapes is often disrupted in cancer. Clonal and subclonal mutations targeting a wide range of molecular functions are frequently observed across cancer types, and emerging evidence suggests that loss of robust epigenetic control promotes both cancer initiation and evolution, independently of context-specific effects. Here, we review how diverse genetic alterations that destabilize the epigenetic regulatory network (ERN) may converge into common phenotypes. We also discuss the implications of altered network topology and systemic epigenetic disorder for the evolution, vulnerability, and therapeutic resistance of cancers.

Whether combination neoadjuvant immunotherapy can enhance response in patients with head and neck cancer remains unclear. Recently, Li et al. demonstrated improved responses with neoadjuvant anti-PD-1+CTLA-4 or anti-PD-1+LAG-3 compared with anti-PD-1 monotherapy. These combination strategies act via different mechanisms with distinct biomarkers of response, highlighting the potential for personalized neoadjuvant immunotherapy approaches.

Space science is reshaping oncology by providing novel insights into cancer biology, diagnostics, and therapeutics. The unique space environment - characterized by microgravity and cosmic radiation - induces profound alterations in cancer cell behavior, immune responses, and tumor microenvironment (TME) interactions. These conditions offer a platform for studying cancer progression, enhancing drug discovery, and refining treatment strategies. This opinion article explores microgravity-induced changes in tumor biology, space-driven advancements in imaging and radiation research, and extraterrestrial contributions to cancer therapeutics. By leveraging these innovations, space research holds transformative potential for improving cancer diagnostics and treatment on Earth.

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.