Trends in Cancer

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The preliminary program for @CellSymposia #CSHallmarks2026 is now live! Explore cutting-edge sessions spanning AI and technology, tumor immunology, system oncology, microbiome, & cancer neuroscience.
#Sitges Nov 1–3, 2026
http://dlvr.it/TQfb1Y

Lipids grease the chain of cancer progression The role of lipids in cancer progression has become a fervent area of exploration. The crosstalk of tumors with adipose tissue is a complex but well-regulated orchestration of signaling pathways, lipid transporters, and enzymes. They regulate fatty acid synthesis, their deposition into lipid droplets (LDs) as triglycerides, induction of lipolysis, shuttling lipids across cells, and their systemic trafficking, modification, and catabolism. For the latter, lipid oxidation has emerged as a metabolic process of particular clinical importance. Products of lipid processing can become secondary messengers, contribute to reactive oxygen species (ROS) generation, stimulate the production of antioxidants, and, if left unchecked, activate cell death pathways including ferroptosis. This review discusses recent updates in the field that are anticipated to have therapeutic implications.

Lipids grease the chain of cancer progression

Targeting persister cells: proactively overcoming therapy resistance in aggressive B cell lymphomas Treatment resistance remains a formidable barrier to curing lymphomas, driven in part by their ability to alter their phenotypic and molecular profiles under therapeutic pressure. A growing body of evidence suggests that a clinically minute population of drug-tolerant persister (DTP) cells, which undergo non-genetic adaptations to survive therapy, are responsible for seeding relapse. We highlight the substantial progress being made to characterize DTP populations, and postulate that they confer novel vulnerabilities for therapeutic targeting. We propose the addition of therapies that proactively address these therapy-induced adaptations to delay or prevent the emergence of resistance in aggressive B cell lymphomas. We contend that this approach can deepen clinical responses, spare patients unnecessary toxicity, and advance progress towards achieving a true cure.

Targeting persister cells: proactively overcoming therapy resistance in aggressive B cell lymphomas

Speed meets precision: rapid intraoperative diagnostics in neuro-oncologic surgery Surgical resection of brain tumors is guided by radiology, anatomical relationships to critical neurological structures, and clinical metrics including patient age and neurological status. Intraoperative decision-making relies on histological assessment through smear and frozen section analysis of tissue; however, such approaches may be insufficient in the era of precision neuro-oncology. Molecular characterization now informs diagnosis, prognosis, and therapeutic response – factors that may directly influence surgical decisions. The integration of novel and rapid intraoperative diagnostic modalities holds the potential to enhance neurosurgical precision, reduce procedure-related morbidity, and maximize the overall effectiveness of modern multimodal brain tumor management.

Speed meets precision: rapid intraoperative diagnostics in neuro-oncologic surgery

Planning for cancer: building accessible and high-quality survivorship care for all Global cancer incidence is rising. In most high-income countries, it is projected that one in two people will be diagnosed with cancer in their lifetime, with incidence rates among middle- and low-income countries also set to follow these projections. Cancer incidence is increasing due to a multitude of factors, including an ageing population, lifestyle factors, and improved detection. Earlier cancer detection and improved treatments mean that people are now living longer with and beyond cancer. Given these occurrences and projections, planning for ‘when’ and not ‘if’ we get cancer is critical. Supportive care in cancer provides high-value return on investment and significantly improves outcomes, yet is clearly underfunded and inconsistently prioritised. Supportive care must be prioritised globally to ensure functioning and wellbeing at all levels of society.

Planning for cancer: building accessible and high-quality survivorship care for all

Exploiting tumor lineage features for precision cancer therapy Cancer cells often retain lineage- and tissue of origin-specific programs established prior to malignant transformation. This observation has been elaborated by advances in single-cell and lineage-tracing technologies, which provide high-resolution mapping of these features. Here, we provide an overview of these recent technological developments and examine how the tissue of origin shapes tumor behavior and vulnerabilities. We discuss how the preferential selection of oncogenic drivers by specific tissues leads to distinct genetic alterations across cancers. We then explore the continued dependence of cancer cells on lineage-specific physiological functions and signaling pathways, thereby revealing lineage-dependent therapeutic targets. Finally, we highlight how lineage-specific cell surface marker expression informs precision immunotherapies. Together, these insights are driving a shift toward therapies tailored to the developmental and functional identities of cancer cells.

Exploiting tumor lineage features for precision cancer therapy

ApCAFs: spatial niches and therapeutic insights across cancers Although interest in antigen-presenting cancer-associated fibroblasts (apCAFs) is increasing, their therapeutic potential remains poorly understood. In a recent study, Chen et al. reveal two osteopontin-expressing apCAF populations present across malignancies and distinct in origin and location: mesothelial-like (M-)apCAFs, which are found near cancer cells, and fibrocyte-like (F-)apCAFs, which associate with lymphocyte-enriched niches.

ApCAFs: spatial niches and therapeutic insights across cancers

HSPC-like blasts in acute lymphoblastic leukemia: biology and therapeutic opportunities Stem cell-like blasts have been associated with hierarchical tumor-initiating potential and poor outcomes in myeloid leukemias. Previous studies using primary samples of acute lymphoblastic leukemia (ALL) have identified blasts that immunophenotypically and transcriptomically resemble hematopoietic stem and progenitor cells (HSPCs), but failed to consistently demonstrate hierarchical tumor-initiating potential in xenograft models. Recent multi-omic profiling of lymphoblastic and mixed-phenotype leukemias has improved our understanding of the phenotypes of HSPC-like blasts and their association with treatment failure, relapse, and lineage switch during therapy. In this review, we highlight the opportunities and challenges of using HSPC-like blasts to risk-stratify patients with ALL and direct patients with relapsed/refractory disease toward targeted therapies.

HSPC-like blasts in acute lymphoblastic leukemia: biology and therapeutic opportunities

Cuproptosis in cancer: from molecular mechanisms to therapeutic intervention Cuproptosis, a recently discovered form of regulated cell death triggered by copper overload, is distinguished by the aggregation of lipoylated mitochondrial proteins and destabilization of iron–sulfur cluster proteins. Given the altered copper metabolism and metabolic dependencies of cancer cells, cuproptosis might represent a unique vulnerability with therapeutic potential. In this review we summarize current knowledge of copper homeostasis, the molecular mechanisms of cuproptosis and its roles in cancer biology. We highlight therapeutic strategies that harness cuproptosis, including copper ionophores, nanomedicine, and rational combination therapies, and discuss challenges such as systemic toxicity, resistance mechanisms, and biomarker development. Finally, we outline key questions and future directions for translating cuproptosis into the clinic.

Cuproptosis in cancer: from molecular mechanisms to therapeutic intervention

Lost but not least: Y chromosome loss as a driver of cancer Traditionally neglected and frequently excluded from large-scale genomic studies, the Y chromosome is now emerging as a potential Achilles’ heel of cancers in men. Recent evidence has suggested that loss of this chromosome – a phenomenon known as loss of Y chromosome (LOY) – is not a silent event, but rather an active driver that promotes tumor progression through loss of tumor suppressor genes, increasing tumor growth and enabling immune evasion. Importantly, LOY creates loss of heterozygosity of paralogous genes on the X chromosome, a vulnerability that can potentially be therapeutically exploited. The exact mechanisms of LOY in cancer, and the utility of LOY as a biomarker and therapeutic target, are open questions for the emerging field of Y chromosome-focused cancer research.

Lost but not least: Y chromosome loss as a driver of cancer

Small-cell lung cancer: anatomy of an immune-cold tumor Small-cell lung cancer (SCLC) is an aggressive neuroendocrine (NE) tumor and a leading cause of cancer-related morbidity. The introduction of immune checkpoint inhibitors (ICIs) transformed the treatment of many other cancers but has so far failed to benefit all but a minority of SCLC patients who gain a modest increase in overall survival. Although SCLC is often considered to be 'immune-cold', there is no consensus mechanistic view on why most patients fail to respond to ICI therapy. We address this important question by reviewing recent genomic profiling studies that reveal a complex immune landscape. Each molecular subtype is associated with a unique pattern of immune infiltration and a program of cellular plasticity that involves loss of NE traits. This immunobiology presents a rapidly evolving case study in mechanisms of ICI response and resistance. We discuss recent developments, present new hypotheses, and explore future directions for the field.

Small-cell lung cancer: anatomy of an immune-cold tumor

Epigenetic drivers of chromosomal instability Chromosomal instability (CIN) fuels phenotypic cancer heterogeneity through heritable epigenetic defects, hence driving disease initiation, progression, and resistance to therapy. Two recent studies, by Bai et al. and Salinas-Luypaert et al., demonstrate that imbalanced histone or DNA methylation actively promotes CIN by disrupting centrosome homeostasis or centromere integrity, globally linking epigenetic dysregulation to mitotic failure and genome instability.

Epigenetic drivers of chromosomal instability

The evolving landscape of brain metastasis: volume II

Orchestrating tumor-immune epigenetics via SERT–H3Q5ser axis

Mapping heterogeneity in the tumor microenvironment of renal cell carcinoma through single-cell omics Renal cell carcinoma (RCC) outcomes are shaped by a complex tumor microenvironment (TME), where malignant cells represent only a minority of the tissue. Recent advances in single-cell technologies – including single-cell RNA sequencing, single-nucleus RNA sequencing, single-cell assay for transposase-accessible chromatin sequencing, single-cell T-cell receptor sequencing, and imaging mass cytometry – have uncovered the cellular, regulatory, and spatial heterogeneity of RCC. Here, we synthesize insights from these approaches to define diverse CD8+ T-cell subsets and exhaustion trajectories, as well as the origins, phenotypic diversity, and functional states of other immune cells including tumor-associated macrophages, dendritic cells, natural killer cells and cancer-associated fibroblasts. Together, these findings highlight the transformative potential of single-cell technologies to unravel TME complexity, identify biomarkers of therapeutic response, and guide precision immunotherapy in RCC.

Mapping heterogeneity in the tumor microenvironment of renal cell carcinoma through single-cell omics

Rethinking fairness in AI to improve current practice in oncology Fairness in artificial intelligence (AI) is often assessed with flawed metrics, particularly in oncology where patient diversity and structural inequities shape outcomes. Ground truth labels, predictions, and demographic attributes all carry biases that distort fairness evaluations. We argue for rethinking fairness frameworks to better capture equity in cancer care.

Rethinking fairness in AI to improve current practice in oncology

Cell Symposia: Hallmarks of cancer

We're excited to host a distinguished lineup of speakers at @CellSymposia #CSHallmarks2026, including keynote speakers @johannajoyce.bsky.social & Faisal Mahmood @harvardmed.bsky.social. View the full speaker lineup: http://dlvr.it/TPbBpN

Chemotherapy-free cancer treatment – not for everyone yet Cytotoxic chemotherapy (CC) has long been the cornerstone of treatment in oncology, but primary resistance, the emergence of secondary resistance, and toxicity remain significant challenges. We explore how precision oncology aims to replace conventional chemotherapy through its enhanced antitumoral activity and reduced toxicity. We highlight significant progress in this area and emphasize recent clinical trials where targeted therapies and immunotherapy have yielded superior outcomes. Despite significant advances in cancer understanding and molecular profiling, in the coming years CC will likely remain a standard treatment for diseases that are not accessible to precision oncology or immunotherapy, as a rescue treatment for many cancers, or in combinations with new agents.

Chemotherapy-free cancer treatment – not for everyone yet

Neural hijacking in cancer metabolism: from nutrients to organelles Tumors dynamically interact with the central and peripheral nervous systems, hijacking neural plasticity and reprogramming metabolism in a bidirectional manner to drive cancer progression. Neural inputs reshape the metabolism of cancer cells and their microenvironment – glycolysis, oxidative phosphorylation, and lipid metabolism – while tumors exploit neuronal nutrients and mitochondria to thrive under metabolic stress. This review explores neurocancer metabolic crosstalk through multiple mechanisms by three principal modes of interaction, highlighting how targeting these metabolic interdependencies could disrupt tumor progression. By integrating cancer metabolism and neuroscience, it offers a conceptual framework for understanding neural-tumor metabolic circuits in malignancy and identifies potential therapeutic vulnerabilities.

Neural hijacking in cancer metabolism: from nutrients to organelles

Interplay between cancer cell lipotypes and disease states While the initial transformation of cancer cells is driven by genetic alterations, tumor cell behaviors and functional states are dynamically regulated by cell-intrinsic factors including proteins, metabolites and lipids, and extrinsic microenvironmental factors. Emerging multi-omics technologies highlighted that cancer cells exhibit distinct lipidome compositions and employ specific lipid metabolic circuits for chemical conversions – collectively defined as ‘lipotypes’. We review the interplay between cancer lipotypes and cellular states, focusing on interpreting how being at different positions along the spectra of representative lipid metabolic axes influences cancerous traits. We aim to instill a system biology perspective to integrate ‘lipotypes’ into the established ‘genotype–phenotype’ framework in cancer.

Interplay between cancer cell lipotypes and disease states

Functional plasticity of RNA-binding proteins in cancer: both friend and foe RNA-binding proteins (RBPs) govern RNA-based post-transcriptional processes that generate the abundance and diversity of the proteome. RBPs have recently emerged as crucial cancer regulators that can influence multiple cancer hallmarks. However, many RBPs display remarkable variations across different tumor types and can exert both tumor-promoting and tumor-suppressive effects. These opposing roles are often attributed to context-dependency, but there is a distinct lack of clarity regarding what aspects of cellular context define the differences in the roles of RBPs. Given the recent development of RBP-targeted interventions, resolving this significant gap in the field could improve the selectivity and specificity of RBP biomarkers and therapies in cancer. This review analyzes recent findings and explores the mechanisms by which the functional plasticity of RBPs in tumorigenesis may arise.

Functional plasticity of RNA-binding proteins in cancer: both friend and foe

Tracing cancer progression through interpretable spatial multi-omics Multi-omics integration is reshaping cancer research by combining histopathology, transcriptomics, and proteomics with spatial and temporal context. Schweizer et al. revealed compartment-specific biology, RNA–protein decoupling, and emergent molecular patterns underpinning malignant transformation in low-grade serous carcinoma, highlighting the potential of integrated multi-omics to uncover novel mechanisms and guide precision oncology.

Tracing cancer progression through interpretable spatial multi-omics

Branched chain amino acids and their aberrant metabolism in cancer Cancer cells require sufficient nutrients to support biomass generation, rapid proliferation, and survival. Thus, extensive reprogramming of amino acid metabolism is necessary for tumor initiation and progression under strenuous conditions. One metabolic pathway that has garnered attention is branched chain amino acid (BCAA) catabolism, a pathway that is highly altered across malignancies. This review examines current insights into how circulating BCAAs and their aberrant catabolic enzymes impact both cancer cells and the surrounding tumor microenvironment.

Branched chain amino acids and their aberrant metabolism in cancer

Tumor-intrinsic dichotomy shapes cellular heterogeneity in pancreatic cancer Intratumoral heterogeneity in pancreatic cancer poses a significant challenge, contributing to disease aggressiveness and complicating treatment. A recent study by Li et al. reveals that this heterogeneity is maintained by tumor-intrinsic reciprocal signaling between SPP1 and GREM1 in the epithelial and mesenchymal cell populations of pancreatic cancer.

Tumor-intrinsic dichotomy shapes cellular heterogeneity in pancreatic cancer

The promise of TIL therapy for glioblastoma Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated efficacy in refractory melanoma and durable responses in lung cancer. Glioblastoma presents distinct challenges for immunotherapy, including profound tumor heterogeneity, low T cell infiltration, and an immunosuppressive microenvironment, but these same features highlight the unique rationale for TILs. Unlike monoclonal engineered approaches, TILs retain natural polyclonality, enabling recognition of a diverse set of tumor-associated antigens and potential adaptation to the evolving antigenic landscape. Preliminary studies have already shown that tumor-reactive TILs can be successfully isolated and expanded from glioblastoma specimens, providing feasibility for clinical translation. This review discusses the current landscape of TIL therapy in glioblastoma, highlights recent advancements, and discusses future directions and clinical translation to position TIL therapy as a promising and adaptable cellular immunotherapy for one of the most treatment-resistant human cancers.

The promise of TIL therapy for glioblastoma

IL17-producing γδ T cells promote radioresistance via immunosuppression

Virus-mediated gene fusion: igniting and sustaining oncogenesis Human papillomavirus (HPV) integration is known to cause host genome instability and subsequent structural variants. Recently, Khan and colleagues thoroughly characterized a recurrent FGFR3-TACC3 fusion caused by HPV integration in oropharyngeal squamous cell carcinoma (OPSCC) identifying synergistic interplay with HPV E6/E7 required for transformation. These findings reveal another mechanism in which virus integration can ignite tumorigenesis and a promising avenue for future investigation.

Virus-mediated gene fusion: igniting and sustaining oncogenesis

Mechanisms of whole-genome doubling in cancer evolution Whole-genome doubling (WGD) has recently emerged as one of the most common genomic alterations in cancer and is associated with genomic instability, drug resistance, and metastasis. However, WGD also generates unique vulnerabilities that create a therapeutic window between cancer cells and healthy cells. Over the past few years, there has been a rapid growth in our understanding of WGD at a molecular level. In this review, we discuss the causes and immediate cellular effects of, and therapeutic considerations for, WGD in cancer.

Mechanisms of whole-genome doubling in cancer evolution

A growing entourage for heterotypic circulating tumor cell clusters Circulating tumor cell (CTC) clusters have emerged as key mediators of cancer spread. Among these, heterotypic CTC clusters exemplify how cooperative interactions between different cell types may enhance metastasis efficiency. Recent studies by Scholten et al. and Schuster et al. uncover additional immune cell partners, including T cells and monocytes, involved in shaping CTC biology.

A growing entourage for heterotypic circulating tumor cell clusters

The very druggable RAS proteins RAS genes encode molecular switches that control cell growth and survival, and their oncogenic mutations drive many cancers. Once deemed ‘undruggable’, RAS is now being challenged by innovative inhibitors. Recent advances, reported by Stanland and Huggins et al. and Feng et al., include EFTX-G12V, an EGFR-directed allele-specific RNAi therapeutic, and MCB-36, a dual-state pan-KRAS degrader, exemplifying precision RAS-targeted strategies.

The very druggable RAS proteins