Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen, progesterone, and HER2 receptors; an aggressive phenotype; high rates of early relapse and metastasis; and the worst mortality rates among all breast cancer subtypes. Currently, there is no effective curative targeted therapy for TNBC and chemotherapy remains the primary treatment for TNBC. Therefore, there is a critical need to develop highly effective, novel therapies to improve patient survival. We previously validated FOXM1, a proto-oncogenic transcription factor, for the first time as a potential molecular target in TNBC through genetic knockdown studies in mice. We show that FOXM1 expression is associated with shorter patient survival and is a marker of poor prognosis. There is no FDA-approved FOXM1 inhibitor. We found that patients with TP53 mutations have dramatically higher FOXM1 expression, indicating that widespread TP53 mutations detected in about 80% of TNBC patients are the major driver of FOXM1 overexpression in TNBC patients. We identified its binding ability using an in silico study, and found it to be a well-known FOXM1 inhibitor that suppresses TNBC cell proliferation, migration, and invasion, and induces apoptosis. In vivo studies in mice bearing TNBC tumors demonstrated that treatment with a novel FOXM1 inhibitor incorporated in single-lipid nanoparticles suppressed the growth of TNBC tumor xenografts. In conclusion, our findings suggest that the novel FOXM1 inhibitor represents a potent and safe therapeutic strategy with significant potential for the treatment of other FOXM1-driven cancers including TNBC that currently have limited treatment options.

Perineural invasion (PNI) is a distinct route of cancer spread associated with neuropathic pain, local recurrence, and poor survival across many solid tumours. Increasing evidence shows that PNI is not only a structural pattern of invasion but also a dynamic biological process involving neurodegeneration, nociceptor sensitisation, and marked local immunosuppression. This narrative review synthesises experimental, translational, and clinical data on the molecular, neurological, and immunological mechanisms of PNI in solid malignancies. PNI arises through complex crosstalk between tumour cells, Schwann cells, macrophages, fibroblasts, and neurotrophic pathways, leading to peripheral nerve remodelling, axonal degeneration, and abnormal regeneration. These changes promote neuropathic pain through ion-channel dysregulation, neurotrophin-driven sensitisation, and pathological neuroplasticity. At the same time, PNI creates an immunosuppressive microenvironment enriched in Tregs, M2 macrophages, and myeloid-derived suppressor cells, shaped by cholinergic, adrenergic, and neuropeptidergic signalling, which may contribute to immune exclusion and resistance to immunotherapy. We propose that PNI should be understood as a neuro-immuno-metabolic process and that recognising the PNI-pain-immunosuppression triad may support the development of targeted neuroprotective, analgesic, and immunomodulatory therapies.

These are the third Canadian consensus guidelines on the management of acute myeloid leukemia (AML) in older patients. The first was published in 2013, and the second in 2017. The management of AML in older patients changed significantly over this time span, with decreasing emphasis on the use of intensive chemotherapy and the adoption of new standards of care based on less-intensive therapies: first azacitidine + venetoclax combinations, followed by azacitidine + ivosidenib. Increased use of these new therapies in older patients has raised questions about their use, including how to determine patient suitability, select the most effective therapy, and manage dosing and toxicity. In this third Canadian guideline, we address these questions to provide clarity around these new standards of care and improve clinician understanding and confidence in using them. As more new targeted agents become available and hypomethylating agent-based triplet combinations are used more widely, we fully anticipate that we will, in some years' time, write a fourth guideline on the management of AML in older patients.

First-line (1L) therapy for mantle cell lymphoma (MCL) continues to evolve rapidly, with several recent phase II and phase III trials consistently showing the activity of novel covalent Bruton's tyrosine kinase inhibitor (cBTKi) combinations. Historical treatment selection criteria such as patient age, fitness, and eligibility for autologous stem cell transplantation generally remain applicable for some, but not all, of these novel regimens. This potential for flexibility necessitates the consideration of additional factors during decision-making, such as MCL biology, patient risk tolerance, logistical and resource implications, and the impact on use of later-line options. This paper presents three illustrative patient cases to explore 1L therapy selection among these new and emerging cBTKi options. The realized and anticipated benefits, limitations, and challenges and persisting evidence gaps associated with these regimens are discussed.

Bile duct tumor thrombus (BDTT) is a rare manifestation of hepatocellular carcinoma (HCC) that causes obstructive jaundice and is associated with a poor prognosis, although a treatment algorithm has yet to be established. We review the treatment landscape for HCC with BDTT, including surgical, transarterial, systemic, and radiotherapy options, and report, to our knowledge, the first case series of magnetic resonance-guided radiotherapy (MRgRT) for this condition. Four patients with unresectable HCC and BDTT were treated on a 0.35-T MR-linac with real-time cine-MRI gating (50 Gy in 5 fractions, n = 3; 40 Gy in 5 fractions, n = 1), with tumor response assessed by modified RECIST. All patients completed treatment without interruption. The best response was complete response in two patients and partial response in two, and obstructive jaundice resolved in both affected patients. The maximum radiation-attributed toxicity was a transient grade 3 bilirubin elevation that resolved without biliary intervention, and no treatment-related deaths occurred. Overall survival ranged from 5.5 to 29 months, with the two Child-Pugh class A patients without portal vein tumor thrombosis surviving 22 and 29 months. MRgRT for HCC with BDTT appears feasible with acceptable short-term safety and merits prospective evaluation.

Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) is the most prevalent subtype of advanced breast cancer and is predominantly driven by estrogen receptor (ER) signaling. Endocrine therapy (ET) has become the backbone of first-line treatment; however, both intrinsic and acquired resistance limit long-term disease control. The introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has fundamentally reshaped the therapeutic landscape even in subsets of patients with aggressive or symptomatic visceral metastatic disease. Advances in molecular profiling have also enabled more precise, adaptive therapy. Circulating tumor DNA (ctDNA)-based liquid biopsy now allows real-time detection of emerging resistance mutations, particularly in ESR1. Additionally, patients with PIK3CA-mutated tumors who had progressed on or within 12 months of completing adjuvant ET and had no prior systemic therapy for metastatic disease had better treatment outcomes when treated with the PI3K inhibitor inavolisib in combination with palbociclib and fulvestrant. Together, these developments mark a shift from fixed treatment sequencing toward a more dynamic, biomarker-driven approach in first-line HR+/HER2- MBC. Integration of CDK4/6 inhibitors with next-generation endocrine agents and liquid biopsy-guided therapy offers the potential to delay resistance, improve survival outcomes, and individualize treatment.

Opioids are frequently prescribed for cancer pain management, yet accumulating evidence suggests that opioid exposure may be associated with inferior outcomes in patients also undergoing treatment with immune checkpoint inhibitors (ICIs). To synthesize mechanistic and clinical evidence linking opioids to the PD-1/PD-L1 axis, the literature was searched up to 18 January 2026, with study selection and data extraction focused on (i) cancer-cell and immune-cell effects of opioid agonism or antagonism on PD-1/PD-L1 biology, and (ii) clinical studies reporting ICI outcomes (progression-free survival, overall survival, or treatment duration) with concomitant opioid exposure. Preclinical studies support multiple, non-mutually exclusive mechanisms: opioids can induce PD-L1 in tumour cells, modulate innate-inflammatory pathways (including TLR4-linked cascades), promote dysfunctional T-cell phenotypes that reduce responsiveness to PD-1 blockade, and show context- and opioid-dependent effects. Clinical cohorts and meta-analytic datasets in non-small cell lung cancer and other tumour types report associations between opioid exposure (including higher morphine-equivalent dosing) and worse ICI outcomes. The intersection of opioid signaling with PD-1/PD-L1 biology likely operates across cancer cell-intrinsic and immune cell-intrinsic pathways, providing a mechanistic rationale for prospective evaluation of opioid-sparing strategies and/or peripheral opioid antagonism as adjuncts to checkpoint blockade.

Lung cancer carries a high psychosocial burden. Tobacco use, the stigma attached to the disease, and coping strategies are thought to interact and shape psychological outcomes, yet they have rarely been examined together. This review aimed to synthesise the evidence on the relationship between tobacco use, lung cancer stigma, and coping, and how these factors interact and influence patients' psychological outcomes.

Following the PRISMA 2020 guideline, PubMed/MEDLINE and Dialnet were searched (window 2014-April 2026) for empirical studies conducted in adults with lung cancer that addressed stigma, coping, or relevant psychological outcomes (e.g., anxiety, depression, distress, or quality of life). Study selection and data extraction were performed independently by two reviewers, with discrepancies resolved by consensus and, where needed, by a third reviewer. Methodological quality was appraised with design-specific tools (JBI for cross-sectional and cohort studies, CASP for qualitative studies, and COSMIN-oriented criteria for the psychometric study). Given the clinical and methodological heterogeneity, a structured narrative synthesis was conducted following the SWiM guideline. The protocol was registered in the Open Science Framework.

Twenty-four studies were included. Stigma was prevalent and consistently associated with depression, anxiety, distress, and poorer quality of life, with longitudinal evidence indicating that stigma precedes and predicts distress. Internalised stigma (guilt, shame, self-blame) was the facet most strongly linked to depression and anxiety. Smoking history graded stigma intensity (current > former > never smokers) but did not determine it, since clinically significant stigma also affected never-smokers. Adaptive coping (e.g., fighting spirit, positive reappraisal) and social support were consistently associated with better psychological adjustment and quality of life, while maladaptive coping (e.g., helplessness, avoidance, anxious preoccupation) was associated with worse outcomes; cross-sectional evidence further indicated that coping modes mediated the relationship between stigma and quality of life and that social support and self-compassion attenuated the impact of stigma on distress.

Internalised stigma is a central, modifiable psychosocial stressor in lung cancer that affects smokers and never-smokers alike. Systematic screening for stigma, coping, and social support, together with non-stigmatising care, is warranted.

Melanoma remains a major global health burden, though immunotherapy and targeted therapy have markedly improved survival. Obesity has paradoxically been associated with favorable outcomes in melanoma, yet body mass index (BMI) alone fails to capture its influence on treatment response. To address this gap, we conducted a multi-site cohort study within the Canadian Melanoma Research Network, including patients with advanced melanoma treated with immunotherapy or targeted therapy. Body composition was quantified using computerized tomography (CT) imaging to assess visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM) mass and intermuscular adipose tissue (IMAT), and associations with progression-free survival (PFS) and overall survival (OS) were evaluated. No overall association was seen for BMI, SAT, VAT, IMAT or SM with PFS or OS. In the targeted therapy subset, higher BMI, SAT, VAT and SM were associated with better OS (hazard ratios 0.56 to 0.65), while no effect was seen in the immunotherapy group. IMAT emerged as a novel prognostic marker, with elevated levels associated with lower OS in males and better OS in females. Our findings show that CT-based body composition is not associated with survival outcomes in patients with advanced melanoma receiving immunotherapy.

Survivors of childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL) are at risk of developing long-term adverse effects after survival. This study examined observed proportions of perceived mental distress, fatigue, and executive function (EF) impairment in adult childhood cancer survivors (CCSs) of ALL, AML, and NHL. Secondly, it examined the association between perceived EF impairment and mental distress or fatigue. Participants (n = 132; 57% female) were recruited from two major Norwegian hospitals. Self-report questionnaires included the Behavior Rating Inventory of Executive Function, Adult Version, the Hopkins Symptom Checklist-25, and the Fatigue Severity Scale. Proportions exceeding established clinical thresholds were calculated, and groups were compared using Pearson's chi-squared test and Newcombe confidence intervals. Overall, 49% and 41% of participants met the clinical thresholds for depression and anxiety; 43% for fatigue; and 28% for EF impairment. Perceived EF impairment was significantly associated with mental distress and fatigue. Mental distress, fatigue, and EF impairment are commonly reported and distressing late effects among CCSs of ALL, AML, and NHL. Follow-up care focusing on neurocognitive and psychological outcomes is important for the long-term functioning and well-being of this survivor group. Targeted neurocognitive rehabilitation may represent a key component of follow-up care.