BACKGROUND: Immune-Checkpoint-Inhibitors (ICIs) have significantly improved the course of advanced/metastatic melanoma and the concept of ICIs curative potential began to appear. To use statistical approaches to determin...BACKGROUND: Immune-Checkpoint-Inhibitors (ICIs) have significantly improved the course of advanced/metastatic melanoma and the concept of ICIs curative potential began to appear. To use statistical approaches to determine whether advanced/metastatic melanoma patients treated with nivolumab alone or in combination with ipilimumab may be considered as functionally cured. METHODS: Individual patient data were reconstructed from published Kaplan-Meier curves of the anti-PD1 arms of the Checkmate-067. The assumption of functional cure was assessed using three approaches based on a flexible-parametric survival model. Once the hypothesis of functional cure was confirmed, the time to functional cure (TTFC) was determined using an intuitive approach based on flexible survival model. RESULTS: The three complementary approaches were consistent and confirmed the functional cure assumption. The TTFC (the shortest time defined by fewer than 1% of patients progressing or dying) was estimated to be 61 (95%CI,50.7;79.4) and 63 m (95%CI,51.1;71.4) for nivolumab alone or in combination, respectively. CONCLUSIONS: We showed that metastatic melanoma patients, treated with the combination or nivolumab alone who were alive and had not progressed by the five-year time-point, can be considered as functionally cured. The robust statistical approach proposed could be applied to other clinical settings when the plausibility of cure is to be validated.
BACKGROUND: Highly vascularised neuroendocrine tumours (NETs) are attractive targets for foslinanib (CVM-1118), which disrupts vasculogenic mimicry and induces apoptosis via tumour necrosis factor receptor-associated pro...BACKGROUND: Highly vascularised neuroendocrine tumours (NETs) are attractive targets for foslinanib (CVM-1118), which disrupts vasculogenic mimicry and induces apoptosis via tumour necrosis factor receptor-associated protein 1. We evaluated the efficacy and safety of CVM-1118 in advanced NETs. METHODS: Patients with grades 1-2, well-differentiated lung, gastrointestinal, or pancreatic NETs, refractory or intolerant to one or more standard therapies and progressing within 6 months, received CVM-1118 (200-300 mg orally twice daily) in 28-day cycles. Primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: Of 43 enroled participants, 35 were efficacy-evaluable; most had grade 2 pancreatic (63%) or gastrointestinal (34%) NETs with two prior therapies. Median PFS was 10.5 months (95% CI, 5.6-22.3). ORR was 3%, DCR was 77%, and median OS was not reached (95% CI, 23.8-NR). Sensitivity analysis in the full analysis set (N = 43) showed a PFS estimate broadly aligned with the primary analysis (median, 8.4 months); patients with prior everolimus, sunitinib, or peptide receptor radionuclide therapy (N = 22; median, 8.3 months) showed similar findings. Treatment-related adverse events occurred in 44%, mostly grades 1-2, with no serious events. CONCLUSIONS: CVM-1118 demonstrates favourable efficacy and safety in advanced NETs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03600233.
BACKGROUND: Small cell lung cancer (SCLC) is a high-grade and aggressive neuroendocrine carcinoma that remains incurable due to the emergence of drug resistance and frequent relapse. This study aimed to clarify the thera...BACKGROUND: Small cell lung cancer (SCLC) is a high-grade and aggressive neuroendocrine carcinoma that remains incurable due to the emergence of drug resistance and frequent relapse. This study aimed to clarify the therapeutic potential and detailed mechanism of altretamine against SCLC. METHODS: Altretamine-triggered cytotoxicity and lipid peroxidation were determined by EdU, FerroOrange probes, etc. GPX4 promoter methylation was evaluated by Methylation-specific PCR, chromatin immunoprecipitation, etc. Altretamine-induced GPX4 degradation was examined by bio-layer interferometry, immunoprecipitation, etc. RESULTS: Altretamine mainly initiates ferroptosis in SCLC cells, accompanied by accumulation of intracellular ROS and lipid peroxidation. Mechanistically, altretamine facilitated the binding of DNMT3A to GPX4 promoter, leading to DNA methylation of GPX4 gene and subsequent transcriptional repression. Moreover, altretamine directly bound to GPX4 protein and accelerated the lysosomal degradation of GPX4 protein in a HSC70-dependent manner. Inhibition of DNA demethylation by inactivating Ten-eleven translocation (TET) proteins synergistically strengthened the anti-SCLC activity of altretamine. CONCLUSIONS: Our findings revealed the first time that altretamine induced ferroptotic cell death by promoting DNMT3A-mediated epigenetic silencing of GPX4 gene and HSC70-mediated lysosomal degradation of GPX4 protein in SCLC cells. Altretamine alone or in combination with TET inhibitors is a valuable and credible strategy for the clinical treatment of SCLC.
All-trans retinoic acid (ATRA), a bioactive vitamin A derivative, regulates cellular differentiation by activating retinoic acid receptors (RARs). While ATRA has revolutionised acute promyelocytic leukaemia (APL) treatme...All-trans retinoic acid (ATRA), a bioactive vitamin A derivative, regulates cellular differentiation by activating retinoic acid receptors (RARs). While ATRA has revolutionised acute promyelocytic leukaemia (APL) treatment, its efficacy in non-APL acute myeloid leukaemia (AML) remains limited due to intrinsic resistance mechanisms, including aberrant epigenetic states and signalling pathways. This review summarises recent mechanistic and translational advances in ATRA-based combination therapies that target differentiation blockade. We focus on the interplay between retinoic acid signalling, chromatin regulation, cell cycle control, and apoptosis, with a particular emphasis on AML. Epigenetic regulators, including the lysine-specific demethylase LSD1 (KDM1A) and the acetyltransferase GCN5 (KAT2A), together with dysregulated cell cycle control and oncogenic signalling, including Fms-like tyrosine kinase 3 (FLT3) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), sustain proliferation and block differentiation. Targeting these pathways with specific inhibitors synergises with ATRA to restore myeloid maturation, induce cell cycle arrest, and promote apoptosis. Future studies should identify predictive biomarkers for patient stratification to translate these synergistic concepts into clinical benefit.
BACKGROUND: Cancer is a major cause of mortality after solid organ transplantation (SOT). Quantifying this risk is difficult due to heterogeneous reports and methodological limitations. METHODS: We conducted a population...BACKGROUND: Cancer is a major cause of mortality after solid organ transplantation (SOT). Quantifying this risk is difficult due to heterogeneous reports and methodological limitations. METHODS: We conducted a population-based cohort study linking data between the UK Transplant Registry, National Cancer Registry, Civil Registration of Deaths, and Hospital Episode Statistics for all SOT recipients in England between 1st June 1992 and 31st December 2015. FINDINGS: Among 50,762 SOT recipients, 22,361 deaths were recorded, of which 3550 (15.9%) were due to cancer, making it the second leading cause of mortality. Overall cancer (excluding non-melanomatous skin cancer) standardised mortality ratio (SMR) was 2.12 (95% CI: 2.05-2.19). Cancer mortality was highest among lung recipients (SMR 3.49; 95% CI: 2.96-4.06), and lowest in kidney recipients (SMR 2.00; 95% CI: 1.92-2.08). Non-Hodgkin's Lymphoma had highest mortality after SOT (SMR 9.86; 95% CI: 9.01-10.75) and was elevated across all transplant types. However, liver and kidney cancer mortality was disproportionately elevated among liver (SMR: 9.30; 95% CI: 7.53-11.24) and kidney transplant recipients (SMR: 5.11; 95% CI: 4.34-5.93), respectively. Several cancers showed no increased mortality. INTERPRETATION: De novo cancer remains a major cause of long-term mortality after SOT in England, with risk stratified by cancer and/or allograft.
Romanos-Nanclares A, Bui LP, Rosner BA
… +4 more, Willett WC, Holmes MD, Chen WY, Eliassen AH
Br J Cancer
· 2026 Jun · PMID 42380484
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BACKGROUND: In 2019, the EAT-Lancet commission defined a "planetary health diet", a combination of food groups and ranges of food intakes that would simultaneously optimize human health and environmental sustainability....BACKGROUND: In 2019, the EAT-Lancet commission defined a "planetary health diet", a combination of food groups and ranges of food intakes that would simultaneously optimize human health and environmental sustainability. We aimed to evaluate adherence to the Planetary Health Diet Index (PHDI) and breast cancer incidence. METHODS: We followed 68,254 participants in the Nurses' Health Study (NHS; 1986-2018) and 93,283 in the Nurses' Health Study II (NHSII; 1991-2019). The PHDI was calculated every 4 y using a validated, semiquantitative food frequency questionnaire. Hazard ratios (HRs) were calculated using multivariable proportional-hazards models. RESULTS: During 4,182,897 person-years of follow-up, we documented 10,378 invasive breast cancer cases. Women in the highest, compared to lowest, PHDI quintile (Q) were at lower breast cancer risk (HR = 0.89; 95% CI: 0.84, 0.95; P-trend<0.01) even after adjusting for weight change. Although heterogeneity by estrogen receptor (ER) status was nonsignificant, the strongest association was observed for estrogen receptor (ER) negative tumors (HR = 0.79; 95% CI: 0.66, 0.93; P-trend = 0.01). CONCLUSIONS: Adhering to a diet that supports both human and planetary health was associated with lower breast cancer risk, particularly ER-negative tumors. Strategies to reduce breast cancer incidence should emphasize the win-win opportunities for a high planetary health diet.
Br J Cancer
· 2026 Jun · PMID 42380483
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Randomised trials established that low-dose CT screening reduces lung cancer mortality over a decade ago. However, population programmes remain limited, even in high-income countries. Lung cancer disproportionately affec...Randomised trials established that low-dose CT screening reduces lung cancer mortality over a decade ago. However, population programmes remain limited, even in high-income countries. Lung cancer disproportionately affects socioeconomically disadvantaged populations. As screening expands, will equity be prioritised? Australia's programme illuminates a promising pathway, but the question remains: can reductions in mortality be achieved equitably?
Meagher NS, White KK, Wilkens LR
… +43 more, Anton-Culver H, Bandera EV, Carney ME, Cramer DW, Cushing-Haugen KL, DeFazio A, Doherty JA, Gentry-Maharaj A, Goode EL, Goodman MT, Harris HR, Karlan BY, Kaufmann SH, Kelemen LE, Köbel M, Koziak JM, Le Marchand L, Lester J, McGuire V, Menon U, Modugno F, Moysich KB, Pearce CL, Pharoah PDP, Pike MC, Qin B, Risch HA, Rothstein JH, Sarink D, Sieh W, Steed H, Terry KL, Thompson PJ, Titus LJ, Van Gorp T, Whittemore AS, Winham SJ, Jordan SJ, Wu AH, Webb PM, AOCS Group, Peres LC, Merritt MA
Br J Cancer
· 2026 Jun · PMID 42373846
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BACKGROUND: Prior studies have examined survival in patients with epithelial ovarian cancer (EOC); however, few consider race and ethnicity, particularly disaggregating Asian and Native Hawaiian/Pacific Islander women. M...BACKGROUND: Prior studies have examined survival in patients with epithelial ovarian cancer (EOC); however, few consider race and ethnicity, particularly disaggregating Asian and Native Hawaiian/Pacific Islander women. METHODS: We analysed data from 18 Ovarian Cancer Association Consortium studies, including women with EOC from Asian (n = 697), non-Hispanic Black (n = 267), Hispanic (n = 492), Native Hawaiian/Pacific Islander (n = 98) and non-Hispanic White (n = 12,998) racial and ethnic groups. We ran Cox proportional hazards models estimating overall survival by race and ethnicity, adjusting for age, stage, year of diagnosis, and histotype, with fully adjusted models accounting for body mass index, smoking, and postmenopausal hormone use. We also examined associations between hormone-related factors and family history and overall survival by race and ethnicity, testing for heterogeneity. RESULTS: Compared to non-Hispanic White women with EOC, Native Hawaiian/Pacific Islander and non-Hispanic Black women had poorer overall survival (Hazard Ratios, HR = 1.58, 95% CI = 1.16-2.16, and HR = 1.31, 95% CI = 1.12-1.54, respectively). The association was more pronounced for Native Hawaiian/Pacific Islander women with high-grade serous carcinoma (HR = 2.00, 95% CI = 1.37-2.92). There was no significant heterogeneity in the associations between epidemiological factors and survival by racial and ethnic groups (p ≥ 0.31). DISCUSSION: Native Hawaiian/Pacific Islander and non-Hispanic Black women with EOC had poorer survival, highlighting the need to address disparities in outcome.
Yoon HS, Shu XO, Wu J
… +8 more, Sanderson M, Wang X, Wen W, Courtney R, Yang JJ, Blot WJ, Zheng W, Cai Q
Br J Cancer
· 2026 Jun · PMID 42373845
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BACKGROUND: Despite the importance of metabolic reprogramming in prostate cancer initiation and progression, little is known about metabolic features associated with prostate cancer risk among Black Americans. METHODS: T...BACKGROUND: Despite the importance of metabolic reprogramming in prostate cancer initiation and progression, little is known about metabolic features associated with prostate cancer risk among Black Americans. METHODS: This nested case-control study included 195 incident prostate cancer cases and 379 matched controls, focusing on Black Americans from the Southern Community Cohort Study. Using pre-diagnostic plasma samples, a global, semi-quantitative metabolomics assay was conducted. Multivariable-adjusted conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for prostate cancer risk associated with a one standard-deviation increase in log-transformed metabolite levels. RESULTS: A total of 26 metabolites were associated with incident prostate cancer at p < 0.01. Of them, seven metabolites were independently associated with prostate cancer risk after mutual adjustment, including S-adenosylhomocysteine (SAH; OR [95% CI] = 0.69 [0.55-0.88]), 14-HDoHE/17-HDoHE (1.46 [1.17-1.83]), 1-linoleoyl-GPI (18:2)* (0.73 [0.57-0.92]), Sphingomyelin (d17:1/16:0, d18:1/15:0, d16:1/17:0)* (1.28 [1.03-1.59]), Gamma-glutamyl-epsilon-lysine (1.45 [1.14-1.85]), and 2,2'-Methylenebis(6-tert-butyl-p-cresol) (0.62 [0.40-0.95]). SAH and 14-HDoHE/17-HDoHE were exclusively linked to aggressive prostate cancer, while the other five metabolites were primarily associated with non-aggressive forms. CONCLUSIONS: We found several circulating metabolites as potential biomarkers for prostate cancer risk among Black Americans. Further large-scale studies are warranted to confirm our findings and to elucidate potential mechanisms.
Mongiovi JM, Babic A, Sasamoto N
… +14 more, Townsend MK, Vitonis AF, Barnard M, Hecht J, Soong TR, Conejo-Garcia JR, Peres LC, Schildkraut JM, Harris HR, Doherty JA, Modugno F, Fridley BL, Tworoger SS, Terry KL
Br J Cancer
· 2026 Jun · PMID 42365137
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BACKGROUND: Non-hormonal intrauterine devices (IUDs) create an inflammatory uterine environment while oral contraceptives (OC) suppress ovulation and have different associations with ovarian cancer risk. We have evaluate...BACKGROUND: Non-hormonal intrauterine devices (IUDs) create an inflammatory uterine environment while oral contraceptives (OC) suppress ovulation and have different associations with ovarian cancer risk. We have evaluated the associations of these two contraceptive exposures with ovarian tumor immune infiltration. METHODS: This study assessed associations of IUD and OC use with tumor immune features via multiplex immunofluorescence in 24 ovarian tumor tissue microarrays from four case-control and two cohort studies. Multivariable-adjusted beta-binomial models estimated the odds of tumor T cell positivity by contraceptive history. RESULTS: High-grade serous tumors had the highest percentage of tumor cells positive for total T cells (CD3 mean=3.4%, SD = 6.1) and each T cell subtype. Ever (vs. never) IUD use was modestly associated with increased cytotoxic T cell infiltration (CD3CD8 OR:1.14, 95% CI:0.99-1.32), which was stronger among those with a history of endometriosis, postmenopausal women, and smokers. Conversely, OC use ≥1 year (vs. never) was associated with lower cytotoxic T cell odds (CD3CD8 OR:0.89, 95% CI:0.79-1.00; p-het=0.008). Increased odds of terminal T cell exhaustion were observed for IUD use only (CD3PD1TIM3 OR:1.53, 95% CI:0.99-2.36), which was stronger among those who had ever used genital powder or BMI > 25 kg/m. CONCLUSIONS: Pre-diagnostic contraception use may influence ovarian tumor immunity and may modulate cancer susceptibility.
Chen F, Chen Y, Sun W
… +7 more, Ma H, Liang Y, Li Y, Li J, Cao X, Ouyang S, Dai L
Br J Cancer
· 2026 Jun · PMID 42365136
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BACKGROUND: Tumour associated autoantibody (TAAb) generated against cell membrane receptor proteins in lung cancer have attracted attention. Understanding the role of these autoantibodies in tumours may open up new thera...BACKGROUND: Tumour associated autoantibody (TAAb) generated against cell membrane receptor proteins in lung cancer have attracted attention. Understanding the role of these autoantibodies in tumours may open up new therapeutic modalities. METHODS: Plasma samples from 1170 participants were used to detect TAAbs level by enzyme-linked immunosorbent assay (ELISA) for evaluating the diagnostic value of candidate TAAbs. 353 non-small cell lung cancer (NSCLC) cases were used to assess the prognostic value of anti-platelet-derived growth factor receptor alpha (PDGFRα) autoantibody. The impact and mechanisms of anti-PDGFRα autoantibody were explored through antibody absorption, CCK-8, transwell, wound healing, and angiogenesis assays in NCI-H1703 cell. RESULTS: Anti - PDGFRα autoantibody was overexpressed in NSCLC and had an AUC of 0.747 (95% CI: 0.701-0.794) for early diagnosis compared to normal individuals. Cox regression analysis showed that it could be served as an independent predictor of poor prognosis in NSCLC with a HR of 1.510 (95% CI: 1.094-2.098). In vitro results suggested a role of anti-PDGFRα in promoting proliferation, migration, and angiogenesis via PI3K/AKT/NF-κB pathway. CONCLUSIONS: Anti-PDGFRα autoantibody is a novel biomarker for early diagnosis and poor prognosis of NSCLC. The mechanisms exploration may provide the theoretical basis for the precision treatment of NSCLC targeting anti-PDGFRα autoantibody.
Dibden A, Parmar D, Gabe R
… +4 more, Smith RA, Moss SM, Johns LE, Duffy SW
Br J Cancer
· 2026 Jun · PMID 42362870
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BACKGROUND: Population-based mammographic screening programmes have been operating for over 30 years and whilst many studies have assessed the short- to medium-term effectiveness of screening, few have assessed their lon...BACKGROUND: Population-based mammographic screening programmes have been operating for over 30 years and whilst many studies have assessed the short- to medium-term effectiveness of screening, few have assessed their long-term effectiveness. The aim of this study was to assess the long-term effectiveness of the NHS Breast Screening Programme in England and Wales. METHODS: 2,509,384 women aged 49-64 years and uninvited to screening upon study entry were studied, with screening status changing on invitation and attendance. Women were followed for breast cancer diagnosis and death for a maximum of 33 years. Poisson regression was used to assess the effect of screening on breast cancer incidence and mortality compared to an uninvited comparison group, and overdiagnosis. RESULTS: After adjustment for confounders, invitation to screening was associated with a 28% reduction in breast cancer mortality (RR: 0.72; 95% CI: 0.71-0.74) and attendance at screening was associated with a 33% reduction (RR: 0.67; 95% CI: 0.65-0.69). There was a 4% excess of breast cancer diagnoses associated with being screened (RR: 1.04; 95% CI: 1.02-1.07) with at least 5 years follow-up post-screening. CONCLUSION: These findings indicate that screening continues to be effective in reducing breast cancer mortality many years after cessation of screening and that the level of overdiagnosis associated with long-term follow-up is low.
Zheng K, Rao K, Lu X
… +4 more, Yang M, Wu H, Ai Z, He J
Br J Cancer
· 2026 Jun · PMID 42362869
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BACKGROUND: Ten-eleven translocation 2 (TET2) is initially identified as a mammalian DNA dioxygenase to orchestrate expression of numerous genes and diverse interplays of physiological and pathological processes. Beyond...BACKGROUND: Ten-eleven translocation 2 (TET2) is initially identified as a mammalian DNA dioxygenase to orchestrate expression of numerous genes and diverse interplays of physiological and pathological processes. Beyond its canonical role, the moonlight functions of TET2 have been gradually uncovered. METHODS: RNA-seq, qPCR and western blot are employed to validate expression of genes. ChIP and RIP analyses are conducted to test the enrichment of genes. Stable isotope labelled glucose is utilized to analyze the metabolic flux. Xenograft analysis is performed to explore growth of tumour in vivo. RESULTS: TET2 binds to and oxidizes mRNA 5-methylcytosine (m5C) of the transcription factors ATF3 and ATF4, thereby enhancing mRNAs degradation. Deficiency of TET2 rewires de novo serine synthesis and the viability of hepatocellular carcinoma (HCC) cells. Both ATF3 and ATF4 are required to sustain transcription of de novo serine synthesis enzymes and the associated metabolic reprogramming under TET2 loss. Ultimately, ATF3 collaborates with ATF4 to contribute to growth of tumours lack of TET2. Deficiency of TET2 sensitizes HCC tumours to serine restriction. CONCLUSIONS: Our findings not only elucidate a heretofore unrecognized mechanism of transcriptional suppression of de novo serine synthesis enzymes, but also propose a targetable vulnerability of HCC tumours.
Liu C, Fukuda E, Sagiya Y
… +11 more, Tsuru H, Okamoto Y, Morisaki T, Kamatani Y, Okada Y, Suzuki Y, Kanai A, Goshima N, Tanikawa C, Matsuda K, BioBank Japan Project
Br J Cancer
· 2026 Jun · PMID 42350789
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BACKGROUND: Tumour-associated autoantibodies (TAAbs) are promising biomarkers for cancer detection, but their induction and clinical relevance in lung cancer remain unclear. METHODS: Serum samples from 695 individuals we...BACKGROUND: Tumour-associated autoantibodies (TAAbs) are promising biomarkers for cancer detection, but their induction and clinical relevance in lung cancer remain unclear. METHODS: Serum samples from 695 individuals were analysed for TAAb profiling by protein-array screening and two-stage ELISA validation. Diagnostic models were constructed with identified TAAbs and compared with conventional tumour markers. Potential mechanisms, clinical and prognostic features of TAAb seropositivity were analysed and its presence in prediagnostic sera was evaluated to assess the potential for early detection. RESULTS: Six TAAbs for small cell lung cancer (SCLC) and four for lung adenocarcinoma (LUAD) were identified, demonstrating excellent diagnostic performance (AUC > 0.8) and outperforming ProGRP and CEA. TAAb induction correlated with antigen overexpression, somatic mutations and HLA class II amino acid polymorphisms. TAAb panel seropositivity was associated with older age and advanced stage in both subtypes, and predicted poor survival in SCLC but a favourable outcome in advanced LUAD. In prediagnostic sera, the TAAb concentration increased progressively, with detectability up to 2 years before clinical diagnosis. CONCLUSIONS: Distinct TAAb panels were identified for SCLC and LUAD, serving as accurate diagnostic markers that enable early detection and as indicators of prognosis in different clinical contexts.
Metcalfe K, Narod SA, Poll A
… +11 more, Hoey C, Warner E, Baxter NN, Isherwood S, MacDougall E, Zemani N, Yang F, Suwito JS, Quan ML, Akbari MR, RUBY Study Group
Br J Cancer
· 2026 Jun · PMID 42337046
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BACKGROUND: The objective of the study was to evaluate the prevalence of pathogenic variants in 18 cancer predisposition genes in a national cohort of women with breast cancer diagnosed at age 40 or younger. METHODS: Wom...BACKGROUND: The objective of the study was to evaluate the prevalence of pathogenic variants in 18 cancer predisposition genes in a national cohort of women with breast cancer diagnosed at age 40 or younger. METHODS: Women with breast cancer at age ≤40 years were recruited from 33 Canadian centres at diagnosis. Germline genetic testing was performed for 18 genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, STK11, RAD51D, RAD51C, EPCAM, MLH1, MSH2, MSH6, and PMS2). Prevalence of pathogenic variants (PVs) was estimated by age, family history and clinical characteristics. RESULTS: In 805 women, 153 PVs were found (positivity rate 18.6%). Most PVs (63%) were found in BRCA1 (50) or BRCA2 (46). Other PVs were in CHEK2 (24), ATM (13), PALB2 (10), TP53 (5), BRIP1 (1), BARD1 (1), CDH1 (1) and PTEN (1). Higher PV frequencies were found in women with tumours with lobular histology (29.2%), triple negative cancers (27.5%), and bilateral breast cancers (35.7%). CONCLUSIONS: Overall, 18.6% of women with young breast cancer had PVs in 18 genes tested, including 6.8% in a gene other than BRCA1 or BRCA2. Study results suggest that genetic testing should be offered to all women diagnosed breast cancer at the age of 40 or younger.
Thomas Z, Pettaway CA, Alhalabi O
… +2 more, Campbell MT, Johns AC
Br J Cancer
· 2026 Jun · PMID 42337045
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Immunotherapy has demonstrated activity in metastatic penile cancer. Shan and colleagues report encouraging safety, efficacy, and tolerability of perioperative chemoimmunotherapy in advanced disease. While these results...Immunotherapy has demonstrated activity in metastatic penile cancer. Shan and colleagues report encouraging safety, efficacy, and tolerability of perioperative chemoimmunotherapy in advanced disease. While these results are promising, they underscore the urgent need for randomized trials to define the role and timing of immunotherapy in this rare and lethal disease.
Yuan J, Gong J, Peng Z
… +14 more, Liu TS, Xu H, Yang J, Wei J, Jiang H, Deng Y, Wang Y, Qi C, Lyu C, Sun Q, Mu L, Song L, Zhang X, Shen L
Br J Cancer
· 2026 Jun · PMID 42337043
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BACKGROUND: FGFR2 has garnered attention as a promising therapeutic target for gastric cancer (GC) because of its role in GC progression. Infigratinib, an FGFR1-3 selective tyrosine kinase inhibitor, has shown potential...BACKGROUND: FGFR2 has garnered attention as a promising therapeutic target for gastric cancer (GC) because of its role in GC progression. Infigratinib, an FGFR1-3 selective tyrosine kinase inhibitor, has shown potential in preclinical GC models. METHODS: Infigratinib was evaluated in a phase 2 trial for patients with FGFR2-amplified GC or gastroesophageal junction (GEJ) adenocarcinoma who had failed two or more lines of systemic treatment for locally advanced or metastatic disease. A total of 21 patients received 125 mg of infigratinib orally once daily on a "3 weeks on, 1 week off" schedule. RESULTS: Infigratinib showed preliminary antitumor activity in this molecularly selected population, as reflected by a confirmed objective response rate of 23.8% (95% CI, 8.2-47.2) with median progression-free survival of 3.4 months and median overall survival of 6.7 months. The most common grade 3-4 adverse events were elevated aspartate aminotransferase, decreased white blood cell count, and neutropenia. No treatment-related deaths occurred. Exploratory genomic analyses identified alterations in individual patients with disease progression that may be associated with resistance; however, these findings were based on a limited number of cases and should be interpreted as hypothesis-generating. CONCLUSIONS: The findings support continued investigation of FGFR-targeted strategies in FGFR2-amplified GC/GEJ adenocarcinoma, while underscoring the need for larger studies, refined biomarker selection, and deeper characterization of resistance mechanisms. TRIAL REGISTRATION: NCT05019794, Registered 28 July 2021, https://clinicaltrials.gov/study/NCT05019794 .
Guo J, Cai F, Zhang M
… +10 more, Nie X, Cai M, Meng F, Li X, Wei Z, Yang Y, Zhang R, Yao Y, Nie Y, Deng J
Br J Cancer
· 2026 Jun · PMID 42310093
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BACKGROUND: Laminin subunit beta 3 (LAMB3) overexpression has been implicated in cancer progression, but its molecular role in gastric cancer (GC) remains unclear. This study aimed to elucidate how LAMB3 promotes GC mali...BACKGROUND: Laminin subunit beta 3 (LAMB3) overexpression has been implicated in cancer progression, but its molecular role in gastric cancer (GC) remains unclear. This study aimed to elucidate how LAMB3 promotes GC malignancy and identify the underlying signalling pathways. METHODS: The clinical significance of LAMB3 was analysed by bioinformatics and immunohistochemistry (IHC) on tissue microarrays. Correlations with clinicopathological parameters were evaluated using Chi-square or Fisher's exact tests, and prognostic value was assessed by log-rank and multivariate Cox regression analyses. Functional assays, including CCK-8, colony formation, Transwell, and xenograft models, were performed to examine the roles of LAMB3 and its downstream effector. Mechanistic studies involved RNA sequencing (RNA-seq), gain- and loss-of-function experiments, RT-qPCR, RNA immunoprecipitation, and western blotting. RESULTS: LAMB3 was significantly upregulated in GC and correlated with aggressive features and poor prognosis. LAMB3 enhanced GC cell proliferation, migration, and invasion. RNA-seq identified sterile alpha motif domain-containing protein 4 A (SAMD4A) as a critical downstream effector. Silencing SAMD4A suppressed, while its restoration rescued, LAMB3-induced malignancy. Mechanistically, LAMB3 activated PI3K-Akt signalling through SAMD4A-mediated degradation of PHLPP2 mRNA. CONCLUSIONS: This study uncovers a previously unrecognised LAMB3-SAMD4A-PHLPP2 regulatory axis that sustains PI3K-Akt activation and drives GC progression, offering potential prognostic and therapeutic value.
Dannhauser FC, Usher-Smith JA, Massou E
… +2 more, Waller J, Dennison RA
Br J Cancer
· 2026 Jun · PMID 42303832
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BACKGROUND: This study assessed current population views about cancer screening in light of the Covid-19 pandemic, screening programme changes and new technological advances. METHODS: UK adults (aged 18 years), recruite...BACKGROUND: This study assessed current population views about cancer screening in light of the Covid-19 pandemic, screening programme changes and new technological advances. METHODS: UK adults (aged 18 years), recruited via the online platform, Prolific, completed a questionnaire about their views on cancer screening, using eight questions from a 2012 survey (weighted for age and sex, n = 603). We summarised participants' views, explored associations with participant characteristics using logistic regression and compared 2024 and 2012 responses using Chi-square tests. RESULTS: Public enthusiasm for cancer screening in the UK remained high with 93% believing routine screening is almost always beneficial, supported by strong beliefs that finding cancer early means treatment saves lives. Awareness of slow-growing cancers was modest at 51% but has increased since 2012. Nevertheless, most participants still wanted testing for slow-growing and untreatable cancer. Some believed they had received too few screening tests, particularly men, people from ethnic minority backgrounds and those with higher educational attainment. CONCLUSIONS: Our study showed that public appetite for screening persists even as awareness of slow-growing cancers increases, reflecting not only possible knowledge gaps but also trust, values and optimism about future treatments. Future research should explore these factors to support truly informed screening decisions.