bims-tumhet 2026-06-07 papers

Issue of 2026–06–07
six papers selected by
Sergio Marchini, Humanitas Research

Cancer Discov. 2026 Jun 01. 16(6): 1050-1054

The Rising Burden of Early-Onset Cancer: Challenges and Opportunities.

Andrea Cercek, Daniel J Zabransky, Gianluca Mauri, Elizabeth M Jaffee, Alberto Bardelli, Timothy R Rebbeck.

Early-onset cancers are increasing globally, yet traditional research frameworks have yet to inform the epidemiologic and biological underpinnings of this trend. This perspective summarizes the current state of knowledge and prospects for a research agenda spanning epidemiology, exposure science, mechanistic studies, and federated infrastructures to address this emerging challenge.

DOI: https://doi.org/10.1158/2159-8290.CD-26-0328

Cancer Discov. 2026 Jun 01. 16(6): 1041-1043

Spatially Defined Cellular Niches Forged by Tumor-Intrinsic MHCII Redefine Immune Competence in Ovarian Cancer.

Jose R Conejo-Garcia, Denarda Dangaj Laniti.

Using integrated multiomic and spatially resolved single-cell profiling of high-grade serous ovarian cancer, Perez-Villatoro and colleagues show that tumor cell-intrinsic MHC class II (MHCII) expression and the organization of tumor-stroma interface niches are major determinants of endogenous antitumor immune activity and clinical outcome. These data argue against models based solely on bulk immune infiltration and instead support a context-dependent framework in which tumor cell state (particularly MHCII expression), spatial immune topology, and prior therapeutic exposure collectively shape the magnitude and quality of immune pressure during disease evolution. See related article by Perez-Villatoro et al., p. 1100.

DOI: https://doi.org/10.1158/2159-8290.CD-26-0636

Discov Oncol. 2026 Jun 04.

The role of circulating tumor DNA in ovarian cancer.

Yiliminuer Abulajiang, Wang Ming, Yumei Wu.

Ovarian cancer (OC) is one of the most aggressive and lethal cancers of the female reproductive system, with the highest mortality rate among the four major gynecological malignancies. Circulating tumor DNA (ctDNA), as an emerging biomarker, has shown great potential in early screening, minimal residual disease (MRD) monitoring, disease recurrence prediction, and personalized treatment of OC This article reviews the application of ctDNA in OC, exploring its role in early diagnosis, MRD monitoring, recurrence prediction, and personalized therapy. The review also summarizes the current technical challenges and future research directions. Compared to traditional tumor markers, ctDNA offers higher sensitivity and specificity, particularly in detecting early tumors and predicting treatment responses. Although ctDNA holds enormous potential for clinical applications, challenges remain in early-stage detection sensitivity and standardization of detection methods. Future research should focus on optimizing ctDNA detection techniques and integrating it with other biomarkers to promote its broader clinical use.

Keywords: Biomarker; CtDNA; EOC; Liquid biopsy; Personalized medicine

DOI: https://doi.org/10.1007/s12672-026-05333-1

NPJ Precis Oncol. 2026 May 30.

Cyclin E1 overexpression identifies a therapeutically relevant poor prognostic patient subgroup in high-grade serous ovarian cancer.

Cyclin-E1 protein overexpression, including through CCNE1 gene amplification, is recognized as a poor prognostic factor in high-grade serous ovarian cancer (HGSOC) and is a promising predictive marker for investigational therapies targeting cell-cycle checkpoints. However, the demonstration of its clinical utility remains elusive due to inconsistent definitions of protein overexpression and gene amplification. This study characterizes Cyclin-E1 overexpression and CCNE1 amplification prevalence and prognostic value in HGSOC using both original and public clinical cohorts. Fifty-nine percent of tumors overexpressed Cyclin-E1, more than half of which had no evidence of CCNE1 gene amplification. The prevalence of CCNE1 amplification varied across studies and was higher in interventional studies. Patients with Cyclin-E1 positive tumors had poorer outcomes after adjuvant therapy. Platinum-based chemotherapy increased Cyclin-E1 expression. These patients were less likely to benefit from PARP inhibitors (75% are BRCA-wildtype) or mirvetuximab-soravtansine (67% were not FRα-high), highlighting a distinct patient population in need of novel therapies.

DOI: https://doi.org/10.1038/s41698-026-01519-6

Cell. 2026 Jun 04. pii: S0092-8674(26)00522-2. [Epub ahead of print]

Plasma signals of lung tumor promotion for molecular cancer prevention.

Tej Pandya, Maria Zagorulya, Michelle M Leung, Marcellus Augustine, Lydia Y Liu, Aino-Maija Leppä, Ulysse Baruchel, Sin Wi Ng, Tamara Klockner, Miriam Mugabo, Anthony J Griffen, Oleg Blyuss, Chrysante S Iliakis, Amalie Grenov, Kerstin Haase, David C Muller, Ka Hung Chan, Jincheng Wu, Vernon A Burk, Neil Wright, Alix Le Marois, Ekaterina Pazukhina, Sophia Ward, Hubert Slawinski, Marc Pelletier, Cian Murphy, Matthew D Park, Thomas Snoeks, Alejandro Suarez-Bonnet, Simon L Priestnall, Alexandros Hardas, Charlotte Grieco, Ami Archer, Alpkaan Celik, Alejandro Jimenez-Sanchez, Rachel Scott, Hana Zahed, Léa Montégut, Rafael Meza, Clinton H Durney, Stephen Lam, Takahiro Karasaki, Roel C H Vermeulen, Huilei Xu, Pablo Serrano-Fernandez, Tatjana Crnogorac-Jurcevic, Usha Menon, Sophia Apostolidou, Alexey Zaikin, Richard Gunu, Harry J Whitwell, Zhe Huang, Zonglun Li, Xin Hu, Bo Zhu, Liming Li, María-Dolores Chirlaque, Marcela Guevara, P Martijn Kolijn, Aghiles Guenoun, Neeloffer Mookherjee, Mattias Johansson, Ziqiao Wang, Nilanjan Chatterjee, Chao-Hua Chiu, Zhengming Chen, Dana Pe'er, Erik Sahai, Saskia Freytag, Andreas Wack, Marc J Gunter, Miriam Merad, Jianjun Zhang, Christopher Carlsten, Pan-Chyr Yang, Hsuan-Yu Chen, Elizabeth A Platz, Lindsay M LaFave, Karl Smith-Byrne, Mariam Jamal-Hanjani, Kevin Litchfield, Nuno R Nene, Nicholas McGranahan, Eva Grönroos, William Hill, Clare E Weeden, Charles Swanton.

Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8+/claudin4+ alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR, or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.

Keywords: cancer cell of origin; cancer prevention; lung adenocarcinoma; lung cancer initiation; lung cancer prevention; lung cancer risk; plasma proteomics; secretory alveolar niche; tumor promotion

DOI: https://doi.org/10.1016/j.cell.2026.05.005

N Engl J Med. 2026 May 31.

Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer.

RASolute 302 Trial Investigators

BACKGROUND: Current therapies offer limited benefit for patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). Aberrant activation of the RAS pathway is the key driver of PDAC, with oncogenic RAS mutations present in more than 90% of cases. Daraxonrasib is an oral RAS(ON) multiselective, tri-complex inhibitor of the active guanosine triphosphate-bound state of mutant and wild-type RAS.
METHODS: In this phase 3, international, open-label, randomized trial, we randomly assigned patients with previously treated mPDAC to receive daraxonrasib or chemotherapy of the investigator's choice. The dual primary end points were overall survival and progression-free survival in the subpopulation of patients with RAS G12 mutations (the RAS G12 population). Key secondary end points included overall survival and progression-free survival in the overall population (which included patients with RAS G12, G13, or Q61 mutations or with no RAS mutation identified) and objective response and patient-reported quality of life in the RAS G12 and overall populations. Safety was also assessed.
RESULTS: A total of 500 patients, including 91.8% with RAS G12 mutations, were randomly assigned to receive daraxonrasib (248 patients) or chemotherapy (252 patients). The median overall survival in the RAS G12 population was 13.2 months with daraxonrasib and 6.6 months with chemotherapy, and the median overall survival in the overall population was 13.2 months and 6.7 months, respectively; the hazard ratio was 0.40 in both populations (P<0.001). The median progression-free survival in the RAS G12 population was 7.3 months with daraxonrasib and 3.5 months with chemotherapy, and that in the overall population was 7.2 months and 3.6 months, respectively; the hazard ratios were 0.45 and 0.49, respectively (P<0.001 for both comparisons). Adverse events that occurred after the start of treatment were reported in all the patients in the daraxonrasib group and in 97.7% of those in the chemotherapy group; the incidence of adverse events of grade 3 or higher was 61.8% and 69.6%, respectively. Treatment-related adverse events that led to treatment discontinuation occurred in 1.2% of the patients in the daraxonrasib group and in 11.2% of those in the chemotherapy group.
CONCLUSIONS: Among patients with previously treated mPDAC, treatment with daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy. (Funded by Revolution Medicines; RASolute 302 ClinicalTrials.gov number, NCT06625320.).

DOI: https://doi.org/10.1056/NEJMoa2605555