British Journal of Cancer

Ha, Lauren; Signorelli, Christina; Cohen, Jennifer; Neville, Kristen A.; Wakefield, Claire E.; Cohn, Richard J.

doi: 10.1038/s41416-025-02965-ypmid: 40021722

Sheikh, Mahdi; Evison, Matthew

doi: 10.1038/s41416-025-02957-ypmid: 39948239

Treating tobacco dependency in patients diagnosed with cancer delivers substantial benefits; improved overall survival, reduced risk of disease recurrence, less treatment-related adverse events and improved quality of life. This study by Mullen et al provides important data on cost-savings and return on investment from embedding tobacco dependency treatment within cancer care and is a call to arms for equitable access to these treatments for all patients diagnosed with cancer.

Lin, Shin-Chih; Cheng, Yu-Sheng; Lin, Yi-Syuan; Nguyen, Thi My Hang; Chiu, Wen-Tai; Tsai, Ya-Chuan; Chen, Hsing-Yi; Lin, Tsung-Yen; Lin, Shih-Chieh

doi: 10.1038/s41416-025-02938-1pmid: 39956847

BackgroundActivation of androgen receptor (AR) by androgen binding to its ligand-binding domain (LBD) has led to the development of clinical drugs that target androgen biosynthesis or the LBD of AR for the treatment of prostate cancer patients. While these drugs initially offer clinical benefits, the emergence of drug resistance is inevitable after a certain duration of treatment.ObjectivesExploring alternative AR domains or identifying novel mechanisms for AR activation is crucial for advancing prostate cancer therapies.MethodsA systematic bioinformatic analysis identified novel androgen-responsive long noncoding RNAs (lncRNAs) in prostate cancer, which were verified using loss-of-function and gain-of-function strategies in vitro and in vivo.ResultslncZBTB10 or LINC02986 was overexpressed in prostate cancer specimens and correlated with poor clinical outcomes. Mechanistically, our findings elucidate the pivotal role of lncZBTB10 in facilitating AR function by inducing S-palmitoylation. Moreover, the interaction between lncZBTB10 and AR not only fosters but also orchestrates biomolecular condensates within the nucleus driven by a novel RNA-binding domain, particularly in prostate cancer cells. Notably, the overexpression of lncZBTB10 not only promotes tumor growth in vivo but also triggers abiraterone resistance in vitro by inducing AR expression.ConclusionsThese results collectively reveal a novel mechanism by which lncZBTB10 regulates AR function in prostate cancer cells.

Huang, Guangzhao; Chen, Su; Han, Bo; Zhang, Gaowei; Bao, Mingzhe; Paka Lubamba, Grace; Hua, Yufei; Li, Honglin; Liu, Wenwen; Shen, Jiefei; Wang, Lei; Lin, Jie; Tang, Patrick Ming-Kuen; Ding, Zhangfan; Li, Chunjie

Pham, Trang Thao Quoc; Liao, Chung-Ping; Shih, Yi-Hsien; Lee, Woan-Ruoh; Liao, Yi-Hua; Chou, Chia-Lun; Chiu, Yun-Wen; Liu, Donald; Wang, Hao-Chin; Chen, Bo-Jung; Shao, Yu-Hsuan Joni; Yeh, Tian-Shin; Lai, Kuei-Hung; Weng, Hao-Jui

Hong, Chen-Tai; Yang, You-En; Juan, Hsueh-Fen; Chang, Chih-Peng; Wang, Yi-Ching

doi: 10.1038/s41416-025-02955-0pmid: 39984679

BackgroundTumor-associated macrophages (TAMs) in the tumor microenvironment (TME) primarily polarize into the M2-phenotype. Our previous study showed that the small GTPase Rab37 mediates IL-6 trafficking in macrophages for M2 polarization. Here, we uncover an unconventional role of Rab37, independent of vesicle trafficking, in promoting M2 polarization of TAMs.MethodsThe gene profiles in wild-type and Rab37 knockout (KO) bone marrow-derived macrophages (BMDMs) were analyzed using cDNA microarray. The mechanism of Rab37 in regulating the interferon (IFN) pathway was confirmed through in vitro/vivo assays and clinical studies.ResultsType I IFN signaling was highly enriched in BMDMs from Rab37 KO mice. Moreover, Rab37 induction and decreased type I IFN genes were observed in macrophages treated with lung cancer-conditioned medium and epigenetic drugs, indicating an epigenetic regulation of Rab37 in TAMs. Mechanistically, GDP-bound Rab37 interacted with the nuclear localization sequence of STAT1 to sequest it in the cytosol from its transcription activities, thus leading to the downregulation of IFN genes. Clinically, CD163+/Rab37+/STAT1cytosol in TAMs expression signature correlated with advanced tumor stages and poor survival of lung cancer patients.ConclusionsOur findings highlight the cytosolic interaction of Rab37-STAT1 in M2 TAM polarization, with CD163+/Rab37+/STAT1cytosol TAMs as a lung cancer prognosis biomarker.[graphic not available: see fulltext]

van der Kleij, Maud B. A.; Meertens, Marinda; Groenland, Stefanie L.; Kordes, Sil; Bergman, Andries M.; de Feijter, Jeantine M.; Huitema, Alwin D. R.; Steeghs, Neeltje; ,

doi: 10.1038/s41416-025-02954-1pmid: 39934337

BackgroundPrevious studies demonstrated better outcomes for mCRPC (metastatic castration resistant prostate cancer) patients with higher abiraterone exposure (minimal plasma concentration (Cmin) > 8.4 ng/mL), but around 40% of patients experience exposure below this target. Pharmacokinetic (PK)-guided interventions following Therapeutic Drug Monitoring (TDM) could optimise exposure and outcomes. We aimed to evaluate the feasibility and effect on treatment outcomes of abiraterone TDM.MethodsPatients with low exposure levels (Low-group, Cmin < 8.4 ng/mL) got a PK-guided intervention. We compared exposure, adverse event (AE) incidence, time on treatment (ToT) and Prostate-Specific Antigen response rate (PSArr) between the Low-group and Adequate-group.ResultsWe included 167 mCRPC patients, with 56 in the Adequate-group and 111 in the Low-group. Interventions were successful 86% of the time. Exposure between groups became corresponding (Low-group: 7.95 to 20.5 ng/mL, Adequate-group: 20.8 ng/mL, p = 0.72) with comparable AE incidence (17% vs. 23%, p = 0.4). Median ToT and PSArr were similar (351 vs. 379 days, p = 0.35; 61.3% vs. 67.9%, p = 0.51).ConclusionsPK-guided interventions improved above target exposure from 33.5% to 81.4% of patients without additional AEs. While historically, low exposure patients had significantly shorter survival, PK-guided interventions eliminated this disparity. As interventions are effective, low-cost and safe, TDM for abiraterone should be considered to enhance treatment outcomes.

Bundred, James; Lal, Nikhil; Chan, Dedrick K. H.; Buczacki, Simon J. A.

doi: 10.1038/s41416-025-02949-ypmid: 39953281

BackgroundWe interrogated two large national databases to explore the underlying mechanisms and institutional effects of the known association of enhanced survival with a higher lymph node yield (LNY) in non-metastatic colon cancer.MethodClinical and pathological data for stage I-III colon adenocarcinomas were extracted from the CORECT-R (England, 2010–2020) and SEER database (USA, 2000–2020). A lymph node (LN) cut-off for the lack of clinically significant increase in nodal positivity was identified. A multivariable Cox-regression model was developed to study the effect of LNY on overall survival. Furthermore, institutional variations in LNY and their impact on survival were explored.ResultsPatients were retrospectively included from the CORECT-R (n = 84,116) and SEER (n = 287,974) databases. No significant increase in nodal positivity was noted after a LN cut-off of 9. However, improved survival was noted in node-negative and node-positive cancers beyond this cut-off. A 1% risk-reduction concerning overall survival was reported for every node counted. We identified ten outlying institutions across England with an observed LNY greater or less than the expected, with no impact on overall survival.DiscussionsWe advocate incorporating LNY into patient and clinician discussions as a surrogate marker of tumour biology and prognosis rather than using LNY as a quality indicator.

Inoue-Choi, Maki; Ramirez, Yesenia; O’Connell, Caitlin; Berrington de Gonzalez, Amy; Dawsey, Sanford M.; Abnet, Christian C.; Freedman, Neal D.; Loftfield, Erikka

doi: 10.1038/s41416-025-02953-2pmid: 39972189

BackgroundDrinking maté, a type of tea consumed at a very hot temperature in South America has been considered as a risk factor for oesophageal squamous cell carcinoma (ESCC).MethodsWe assessed daily intake and preferred temperature of hot beverages (tea and coffee) in relation to incident ESCC (n = 242) and adenocarcinoma (EAC; n = 710) among 454,796 adults in the UK Biobank. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression.ResultsRelative to non-drinkers and warm temperature drinkers (referent group), drinking 4–6 cups/d (HR, 1.97; 95% CI, 1.14–3.38) or more of hot temperature beverages was associated with higher risk of ESCC; HRs increased with increasing daily intake of hot temperature beverages (P-trend < 0.01). ESCC risk was still higher for those who drank very hot beverages; drinking ≤ 4 cups/d was associated with a 2.5-fold higher risk (HR, 2.52; 95% CI, 1.27–5.03), and risk increased with increasing daily intake of very hot temperature beverages (P-trend < 0.01). There was no clear association for EAC.ConclusionsOur findings provide new evidence that drinking hot or very hot beverages is a risk factor for ESCC in the UK where drinking hot tea and coffee is common.

Elomaa, Hanna; Tarkiainen, Vilma; Äijälä, Ville K.; Sirniö, Päivi; Ahtiainen, Maarit; Sirkiä, Onni; Karjalainen, Henna; Kastinen, Meeri; Tapiainen, Vilja V.; Rintala, Jukka; Meriläinen, Sanna; Saarnio, Juha; Rautio, Tero; Tuomisto, Anne; Helminen, Olli; Wirta, Erkki-Ville; Seppälä, Toni T.; Böhm, Jan; Mäkinen, Markus J.;