Trends in Cancer

Disarming cancer resistance: FAK as a therapeutic target

FGFR rearrangements: oncogenic drivers and therapeutic targets

Nociceptive neuroimmune circuit drives immune evasion Tumor-associated sensory nerves are emerging regulators of cancer immunity, yet their role in systemic immunosuppression remains unclear. Zhang et al. revealed that tumors hijack an interorgan nociceptor–slit guidance ligand 2–calcitonin gene-related peptide circuit to escape immune surveillance. Disrupting this neural loop restores T-cell function and enhances immunotherapy efficacy.

Nociceptive neuroimmune circuit drives immune evasion

Submit your abstract here

Abstracts are invited for @CellSymposia #CSHallmarks2026, Sitges, Spain, Nov 1–3, 2026.

Submit by June 26 for the chance to share your insights with a global audience committed to translating science into life-saving therapies.
http://dlvr.it/TRGjdv

MAX in cancer: dynamic role of MYC’s partner-in-crime MAX is the essential binding partner of MYC, necessary for MYC-dependent transcriptional activation. Depending on the context, MAX can function as a tumor suppressor or promote tumorigenesis in an MYC-driven manner. Here, we highlight the key discoveries defining the role of MAX in cancer and the current research gaps.

MAX in cancer: dynamic role of MYC’s partner-in-crime

Melanoma-secreted melanosome-MHC I disrupts T cell antitumor immunity

ALPK1 agonists ignite innate immunity in anticancer therapy A recent study published in Nature by Tian et al. identifies UDSP-Hep as a synthetic agonist of the innate immune receptor Alpha-protein kinase 1 (ALPK1) that induces enhanced antitumor activity compared with the canonical ALPK1 agonist ADP-Hep and Toll-like receptor or stimulator of interferon genes agonists. UDSP-Hep drives the tumor microenvironment toward a proinflammatory, antitumor state.

ALPK1 agonists ignite innate immunity in anticancer therapy

Evolving approaches to broaden public and patient involvement in cancer research Public and Patient Involvement (PPI) integrates patients and the public into research design, conduct, and dissemination to ensure future research represents the needs of society. We propose a toolkit for researchers, based on outcomes from an ovarian cancer PPI project, to incorporate meaningful, representative cancer research into future studies.

Evolving approaches to broaden public and patient involvement in cancer research

Mechanistic cancer prevention comes of age Historically underfunded and dominated by epidemiological and behavioural research, cancer prevention is now able to embrace mechanistic insights that enable targeted, biologically grounded interventions. As a new generation of mechanistically based strategies begins to take shape, cancer prevention is poised to enter a new era.

Mechanistic cancer prevention comes of age

Lung cancer in never smokers: from early detection to prevention Lung cancer in never smokers (LCINS) is a growing global health challenge. Unlike smoking-related lung cancer, LCINS is characterized by distinct epidemiological patterns and unique molecular pathogenesis and, consequently, requires different clinical management approaches. Unfortunately, for patients with lung cancer who have never smoked, symptoms are nonspecific and often dismissed due to these patients not fitting a high-risk profile (e.g., smoker), underscoring the need for improved detection and interception. Emerging risk factors, including germline variants, clonal hematopoiesis, and environmental exposures, offer new avenues for risk stratification and preventive strategies. While low-dose computed tomography screening shows promise in high-risk subgroups, challenges remain in optimizing cost-effectiveness. Novel prevention approaches, from interleukin (IL)-1β inhibition to cancer vaccines, are under investigation. This opinion article discusses why LCINS demands unique clinical and research paradigms to address its biological complexity.

Lung cancer in never smokers: from early detection to prevention

Dimensions of cancer

In this @cp-cell.bsky.social review, Doug Hanahan shows how the Hallmarks of cancer framework has evolved over the last 25 years: http://dlvr.it/TQkrlD

We'll discuss this in depth @CellSymposia #CSHallmarks2026 http://dlvr.it/TQkrlJ

Submit your abstract here

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