Early-onset colorectal cancer is rising globally. This Roadmap examines current knowledge gaps in risk factors, proposes an integrative conceptual model for risk factor discovery and prevention, and highlights the role of transdisciplinary science and patient engagement in reversing the trend.

Replication stress drives genomic instability, tumour evolution and therapeutic adaptation, yet also creates exploitable vulnerabilities. In this Review, Chen and Zou discuss how chronic replication stress shapes cancer biology and how emerging therapies are targeting the pathways that enable tumour cells to survive it.

Despite remarkable advances in our understanding of breast cancer biology and in the diagnosis and treatment of the disease, outcomes remain deeply influenced by where people live, how health systems function and whether care pathways are effectively coordinated. In this Comment, Miriam Mutebi outlines how we can translate innovation into equitable patient benefits.

Viral mimicry is the activation of antiviral immune responses by endogenous nucleic acids that have accumulated in the cytosol. In this Review, Chen et al. highlight how cancer-associated epigenetic and transcriptional dysregulation promotes the generation of immunogenic nucleic acids, which can limit tumour progression. They further outline the mechanisms tumours use to suppress these responses, and the evidence that escape from viral mimicry is central to tumour evolution and a potential target for therapy.

Nature Reviews Cancer, Published online: 22 September 2026; doi:10.1038/s41568-026-00979-zReplication stress drives genomic instability, tumour evolution and therapeutic adaptation, yet also creates exploitable vulnerabilities. In this Review, Chen and Zou discuss how chronic replication stress shapes cancer biology and how emerging therapies are targeting the pathways that enable tumour cells to survive it.

Population genetics provides a quantitative framework for interpreting cancer genomes as records of tumour evolution. This Review outlines how models of mutation, selection and drift enable inference of tumour dynamics from sequencing data, distinguish genetic and non-genetic processes, and support extraction of evolutionary trajectories beyond pattern-based statistical genomics.

Nature Reviews Cancer, Published online: 22 September 2026; doi:10.1038/s41568-026-00980-6This Editorial marks the 25th anniversary of Nature Reviews Cancer. On this milestone we contemplate how our view of cancer has changed over the past 25 years and speculate on what the future holds.

In this Review, Izzo et al. discuss how single-cell multimodal sequencing enables genotype–phenotype mapping and, when combined with phylogenetic reconstruction, provide insights into clonal evolution, cell state plasticity, and cancer progression, revealing mutant-specific vulnerabilities and offering a framework to study somatic evolution across pre-malignant and malignant human tissues.

Neutrophils exhibit context-dependent pro-tumour and antitumour functions in cancer. In this Review, Diehl, Basto et al. examine neutrophil roles in tumour progression and metastasis, drawing parallels with non-cancer contexts and highlight emerging strategies to therapeutically target and reprogramme neutrophil biology in cancer.

Early-onset colorectal cancer is rising globally. This Roadmap examines current knowledge gaps in risk factors, proposes an integrative conceptual model for risk factor discovery and prevention, and highlights the role of transdisciplinary science and patient engagement in reversing the trend.

In this Review, Franceschini and colleagues discuss how remodelling of the 3D structure of chromatin in cancer is both a cause and a consequence of genetic and epigenetic alterations and highlight how chromatin 3D conformation might be exploited for diagnosis and therapy.

Nature Reviews Cancer, Published online: 15 September 2026; doi:10.1038/s41568-026-00977-1Viral mimicry is the activation of antiviral immune responses by endogenous nucleic acids that have accumulated in the cytosol. In this Review, Chen et al. highlight how cancer-associated epigenetic and transcriptional dysregulation promotes the generation of immunogenic nucleic acids, which can limit tumour progression. They further outline the mechanisms tumours use to suppress these responses, and the evidence that escape from viral mimicry is central to tumour evolution and a potential target for therapy.

In this Journal Club, Yolanda Chirino and Estefany Medina-Reyes discuss a study that used mechanistic markers of carcinogenesis to provide early evidence of the potential cancer risks associated with e-cigarette exposure.

Nature Reviews Cancer, Published online: 11 September 2026; doi:10.1038/s41568-026-00982-4Despite remarkable advances in our understanding of breast cancer biology and in the diagnosis and treatment of the disease, outcomes remain deeply influenced by where people live, how health systems function and whether care pathways are effectively coordinated. In this Comment, Miriam Mutebi outlines how we can translate innovation into equitable patient benefits.

Megakaryocytes contribute substantially to the pathogenesis of myeloproliferative neoplasms (MPNs), but therapeutic strategies targeting this lineage are lacking. Wen, Cotton et al. demonstrate that menin inhibition impairs megakaryocyte differentiation, suppresses myelofibrosis and improves disease features across preclinical MPN models.

Nature Reviews Cancer, Published online: 09 September 2026; doi:10.1038/s41568-026-00973-5Population genetics provides a quantitative framework for interpreting cancer genomes as records of tumour evolution. This Review outlines how models of mutation, selection and drift enable inference of tumour dynamics from sequencing data, distinguish genetic and non-genetic processes, and support extraction of evolutionary trajectories beyond pattern-based statistical genomics.

Many advances in cancer treatment depend on discoveries made decades earlier. In this Comment, Murphy et al. discuss the histories of EGFR, HER2, CDK4/6 and RAS, highlighting how long translation can take and how clinical benefit can continue to accumulate as more effective drugs are developed, used in earlier disease settings and combined with existing treatments.

Nature Reviews Cancer, Published online: 08 September 2026; doi:10.1038/s41568-026-00970-8In this Review, Izzo et al. discuss how single-cell multimodal sequencing enables genotype–phenotype mapping and, when combined with phylogenetic reconstruction, provide insights into clonal evolution, cell state plasticity, and cancer progression, revealing mutant-specific vulnerabilities and offering a framework to study somatic evolution across pre-malignant and malignant human tissues.

Nature Reviews Cancer, Published online: 08 September 2026; doi:10.1038/s41568-026-00974-4To mark the 25th anniversary of Nature Reviews Cancer, six researchers reflect on the conceptual advances that have reshaped cancer research — from somatic mosaicism, functional genomics and cancer stem cells to tumour metabolism, precision oncology and artificial intelligence — and consider which ideas transformed the field, which fell short of expectations, and what challenges remain.

Nature Reviews Cancer, Published online: 07 September 2026; doi:10.1038/s41568-026-00968-2Neutrophils exhibit context-dependent pro-tumour and antitumour functions in cancer. In this Review, Diehl, Basto et al. examine neutrophil roles in tumour progression and metastasis, drawing parallels with non-cancer contexts and highlight emerging strategies to therapeutically target and reprogramme neutrophil biology in cancer.

Nature Reviews Cancer, Published online: 07 September 2026; doi:10.1038/s41568-026-00975-3To mark the 25th anniversary of Nature Reviews Cancer, six emerging cancer researchers share their perspectives on the future of the field, highlighting conceptual opportunities, challenging established paradigms and identifying the approaches they believe will drive progress in the field over the next 25 years.

Nature Reviews Cancer, Published online: 02 September 2026; doi:10.1038/s41568-026-00981-5Megakaryocytes contribute substantially to the pathogenesis of myeloproliferative neoplasms (MPNs), but therapeutic strategies targeting this lineage are lacking. Wen, Cotton et al. demonstrate that menin inhibition impairs megakaryocyte differentiation, suppresses myelofibrosis and improves disease features across preclinical MPN models.

Immunotherapy remains largely ineffective in gliomas despite success in other cancers. In this Review, Engelhardt and Platten outline how central nervous system immune privilege is enforced by specialized brain barriers that restrict T cell surveillance and discuss strategies to overcome these barriers to improve T cell-based immunotherapy for glioma.

Nature Reviews Cancer, Published online: 28 August 2026; doi:10.1038/s41568-026-00978-0Many advances in cancer treatment depend on discoveries made decades earlier. In this Comment, Murphy et al. discuss the histories of EGFR, HER2, CDK4/6 and RAS, highlighting how long translation can take and how clinical benefit can continue to accumulate as more effective drugs are developed, used in earlier disease settings and combined with existing treatments.

Nature Reviews Cancer, Published online: 26 August 2026; doi:10.1038/s41568-026-00965-5Early-onset colorectal cancer is rising globally. This Roadmap examines current knowledge gaps in risk factors, proposes an integrative conceptual model for risk factor discovery and prevention, and highlights the role of transdisciplinary science and patient engagement in reversing the trend.

In this Journal Club, Sandra Romero-Cordoba discusses a study that identifies a replication-associated DNA methylation signature, termed CellDRIFT, providing evidence that epigenetic drift linked to cell division may contribute to oncogenic transformation.

Nature Reviews Cancer, Published online: 26 August 2026; doi:10.1038/s41568-026-00976-2In this Journal Club, Yolanda Chirino and Estefany Medina-Reyes discuss a study that used mechanistic markers of carcinogenesis to provide early evidence of the potential cancer risks associated with e-cigarette exposure.

Nature Reviews Cancer, Published online: 25 August 2026; doi:10.1038/s41568-026-00969-1In this Review, Franceschini and colleagues discuss how remodelling of the 3D structure of chromatin in cancer is both a cause and a consequence of genetic and epigenetic alterations and highlight how chromatin 3D conformation might be exploited for diagnosis and therapy.

Kaleidoscope of colour, inspired by the Review on p661.

Nature Reviews Cancer, Published online: 20 August 2026; doi:10.1038/s41568-026-00960-wImmunotherapy remains largely ineffective in gliomas despite success in other cancers. In this Review, Engelhardt and Platten outline how central nervous system immune privilege is enforced by specialized brain barriers that restrict T cell surveillance and discuss strategies to overcome these barriers to improve T cell-based immunotherapy for glioma.

Nature Reviews Cancer, Published online: 19 August 2026; doi:10.1038/s41568-026-00972-6In this Journal Club, Sandra Romero-Cordoba discusses a study that identifies a replication-associated DNA methylation signature, termed CellDRIFT, providing evidence that epigenetic drift linked to cell division may contribute to oncogenic transformation.

The progression of pancreatic ductal adenocarcinoma (PDAC) from precursor lesions presents an opportunity for cancer prevention. Haldar et al. developed mKRAS-VAX, a peptide vaccine targeting six common KRAS mutations in PDAC, and evaluated it in a phase I clinical trial.

No existing model can reliably predict how an individual cancer will evolve. In this Comment, Guimarães and Reis argue that the future of precision oncology lies not in increasingly sophisticated in vitro tumour models or in artificial intelligence alone, but in the iterative feedback loop between the two.

Nature Reviews Cancer, Published online: 14 August 2026; doi:10.1038/s41568-026-00971-7The progression of pancreatic ductal adenocarcinoma (PDAC) from precursor lesions presents an opportunity for cancer prevention. Haldar et al. developed mKRAS-VAX, a peptide vaccine targeting six common KRAS mutations in PDAC, and evaluated it in a phase I clinical trial.

Tian et al. conducted an observational cohort study utilizing data from biobanks in the UK and USA, finding that more advanced biological ageing compared to chronological age may be a risk factor for early-onset solid cancers with implications for cancer prevention and early interception.

In this Review, Hong and Li explore how defects in DNA damage response (DDR) pathways shape tumour immunogenicity and influence responses to immune checkpoint inhibitors. They highlight shared immunological consequences across distinct DDR alterations, discuss mechanisms of resistance and evaluate therapeutic strategies integrating DDR-targeting agents with immunotherapy to improve clinical outcomes.

Twenty-five years after the launch of Nature Reviews Cancer, the experiences of women in cancer research have changed in important ways, with gains in visibility, representation and recognition. In this World View, Joyce reflects on the progress achieved and the persistent structural barriers that continue to impede equity.

Nature Reviews Cancer, Published online: 03 August 2026; doi:10.1038/s41568-026-00966-4No existing model can reliably predict how an individual cancer will evolve. In this Comment, Guimarães and Reis argue that the future of precision oncology lies not in increasingly sophisticated in vitro tumour models or in artificial intelligence alone, but in the iterative feedback loop between the two.

In this Review, Liu et al. discuss how pyroptosis, executed by a family of pore-forming proteins known as gasdermins, can induce antitumour immunity, which might be therapeutically leveraged for synergy with existing cancer immunotherapies.

Nature Reviews Cancer, Published online: 03 August 2026; doi:10.1038/s41568-026-00967-3Tian et al. conducted an observational cohort study utilizing data from biobanks in the UK and USA, finding that more advanced biological ageing compared to chronological age may be a risk factor for early-onset solid cancers with implications for cancer prevention and early interception.

In this Journal Club, Muñoz-Bello and Lizano discuss the discovery of circE7, a protein-coding circular RNA generated by back-splicing in high-risk HPV that drives E7 expression and tumour growth, revealing a previously unappreciated mechanism of viral oncogene regulation.

Nature Reviews Cancer, Published online: 28 July 2026; doi:10.1038/s41568-026-00958-4In this Review, Hong and Li explore how defects in DNA damage response (DDR) pathways shape tumour immunogenicity and influence responses to immune checkpoint inhibitors. They highlight shared immunological consequences across distinct DDR alterations, discuss mechanisms of resistance and evaluate therapeutic strategies integrating DDR-targeting agents with immunotherapy to improve clinical outcomes.

Nature Reviews Cancer, Published online: 27 July 2026; doi:10.1038/s41568-026-00961-9Twenty-five years after the launch of Nature Reviews Cancer, the experiences of women in cancer research have changed in important ways, with gains in visibility, representation and recognition. In this World View, Joyce reflects on the progress achieved and the persistent structural barriers that continue to impede equity.

Nature Reviews Cancer, Published online: 27 July 2026; doi:10.1038/s41568-026-00959-3In this Review, Liu et al. discuss how pyroptosis, executed by a family of pore-forming proteins known as gasdermins, can induce antitumour immunity, which might be therapeutically leveraged for synergy with existing cancer immunotherapies.