Trends in cancer最新文献

Little is known about lung precancer progression. Recently, Zhu et al. explored the early immunologic landscape of lung adenocarcinoma (LUAD) precursors and identified T cell immunoglobulin and mucin domain 3 (TIM-3) as a putative immune checkpoint target for precancer interception. TIM-3 blockade in mice harboring premalignant lesions delayed progression to invasive adenocarcinoma, suggesting potential clinical utility in high-risk individuals detected through screening.

Menin has emerged as a promising therapeutic target in acute myeloid leukemia (AML). The menin-MLL1 interaction promotes an oncogenic transcriptional program that drives leukemogenesis in HOX-mediated acute leukemias, including KMT2A-rearranged (KMT2Ar), nucleophosmin 1-mutated (NPM1m), and NUP98-rearranged (NUP98r) AML, prompting development of menin inhibitors for treatment of these subtypes. Successes in clinical investigation have led to recent FDA approval of revumenib for KMT2Ar AML, with numerous trials examining menin inhibitors as monotherapy and in combination with other antileukemic drugs ongoing. Although menin inhibitors represent a major advancement in AML treatment, acquired resistance is an evolving barrier to efficacy. Here, we examine the biological rationale for menin inhibition and discuss the landscape of clinical trials and resistance mechanisms associated with menin inhibitors.

Significant advances in matrix biology research have enhanced our understanding of individual matrix components and extracellular matrix (ECM) signalling. The dysregulation of the ECM during the development of solid tumours is a critical area of investigation. Despite recent progress, further investigation into the role of the ECM in cancer progression and therapeutic targeting remains essential for improving outcomes. This study is especially relevant for ECM-rich cancers, such as pancreatic cancer, which is characterised by dense fibrosis that impacts all stages of tumour development, including initiation, progression, and chemoresistance. Currently, no matrix-targeting agents have achieved mainstream clinical implementation. Challenges in this field include insufficient integration of new technologies, and limited understanding of cross disciplinary influences and of the complex, multifunctional nature of the ECM. In this review, we highlight key areas of matrix biology research that are crucial for advancing cancer treatment.

A recent study in Science by Ely et al. identifies immunogenic, cancer-restricted noncanonical HLA-I-bound peptides (ncHLAp) in pancreatic cancer. Using a translation-informed filtering strategy, the study uncovers cryptic antigens derived from unannotated ORFs and validate antigen-specific T cell receptors (TCRs) capable of targeting pancreatic ductal adenocarcinoma (PDAC) in preclinical models, offering new avenues for immunotherapy.

Neuro-tumor crosstalk is reshaping our understanding of cancer. Increasing data demonstrate that calcitonin gene-related peptide (CGRP) is a key neural driver of tumor growth, immune suppression, and cancer-associated symptoms, positioning CGRP-mediated neural addiction as a promising therapeutic target to disrupt tumor-nerve interactions and improve outcomes in patients with cancer.

Cancers are complex, diverse, and elusive, with extrachromosomal DNA (ecDNA) recently emerging as a crucial player in driving the evolution of about 20% of all tumors. In this review we discuss open questions concerning the evolutionary role of ecDNA in tumor development, including tumorigenesis and metastatic seeding, the mutational landscape on ecDNA, the dynamic ecDNA genotype-phenotype map, the structural evolution of ecDNA, and how knowledge of tissue-specific ecDNA evolutionary paths can be leveraged to deliver more effective clinical treatment. Looking forward, evolutionary theoretical modeling will be instrumental in advancing new research in the field, and we explore how modeling has contributed to our understanding of the evolutionary principles governing ecDNA dynamics. Ultimately, these challenges must be tackled to improve clinical stratification and create tumor- and patient-specific ecDNA-based therapies.

Most colorectal cancers (CRCs) are characterized by a low mutational burden and an immune-cold microenvironment, limiting the efficacy of immune checkpoint blockade (ICB) therapies. While advanced tumors exhibit diverse immune evasion mechanisms, emerging evidence suggests that aspects of immune escape arise much earlier, within precancerous lesions. In this review, we discuss how early driver mutations and epigenetic alterations contribute to the establishment of an immunosuppressive microenvironment in CRC. We also highlight the dynamic crosstalk between cancer cells, stromal niche cells, and immune cells driving immune evasion and liver metastasis. A deeper understanding of these early events may guide the development of more effective preventive and therapeutic strategies for CRC.

Impaired cellular metabolism contributes to the age-related decline in T cell function, undermining the response to immunotherapy in older patients with cancer. In a recent study, Hope et al. report that a reduction in intracellular NAD⁺ levels compromises metabolic fitness and drives immunosenescence. Notably, restoring NAD⁺ levels can reverse age-related chimeric antigen receptor (CAR)-T deterioration, suggesting a promising 'metabolic immunotherapy' that widely benefits older patients with cancer.

Gastric cancer arises from complex carcinogenic factor interactions, with limited treatment options due to the lack of targetable driver gene mutations and significant tumor heterogeneity. Recent studies have provided promising novel approaches to improve our understanding of gastric cancer heterogeneity through integrated characterization, combining genomics with emerging technologies. Delineating the molecular changes and targeting specific molecular subtypes will enhance the efficacy of gastric cancer treatment and improve clinical outcomes. This review provides a comprehensive overview of current technologies used in gastric cancer research, highlighting key discoveries and treatment strategies driven by these innovations. Finally, we discuss the emerging technology-guided directions and potential breakthroughs that could enhance the understanding of gastric cancer tumor heterogeneity, ultimately improving clinical outcomes.

Knowledge of cancer development and progression gained over the last few decades has enabled mapping of genetic and epigenetic changes unique to different phases of tumor evolution. Here we focus on epigenetic changes that drive melanoma development and progression. We highlight the importance of epigenetic mechanisms which encompass crosstalk with melanoma microenvironment that affect metastasis and therapy resistance. This review summarizes recent advances and describes potential strategies to leverage this knowledge to devise new therapies.