Current oncology最新文献

Metabolic reprogramming is a defining feature of breast cancer, enabling tumor cells to sustain rapid proliferation, survive under stress, and resist therapy. Key pathways including glycolysis, glutaminolysis, lipid metabolism, and one-carbon metabolism, play central roles in meeting the energetic and biosynthetic demands of malignant cells. Enhanced glycolytic flux supports ATP generation and lactate production, while glutamine metabolism fuels the tricarboxylic acid cycle and provides nitrogen for nucleotide synthesis. Lipid metabolic pathways, particularly fatty acid synthesis, contribute to membrane biogenesis and signaling, and one-carbon metabolism driven by serine and glycine supplies methyl groups for epigenetic regulation and nucleotide production. These metabolic adaptations not only promote tumor growth but also create vulnerabilities that can be exploited therapeutically. Inhibiting these pathways has shown promise in preclinical models; however, challenges such as metabolic plasticity, tumor heterogeneity, and potential toxicity in normal tissues underscore the need for biomarker-driven strategies and rational combination therapies. Herein, we describe current knowledge of the role of these pathways in breast cancer progression, highlighting the role of key enzymes in promoting breast cancer tumor cell growth and in breast cancer prognoses.

Financial hardship affects 30-70% of cancer patients and is associated with worse quality-of-life outcomes and higher mortality. In response, many health systems have implemented financial navigation teams to mitigate financial hardship and provide financial guidance to cancer patients. Currently, there is a lack of standardization in financial navigation training. Our primary objective was to assess current training practices and gaps that may exist in critical information and tools for day-to-day operations for individuals providing financial navigation services. Our secondary objective was to supplement findings from the interviews with a web-based search for training resources that would be helpful in these roles. Semi-structured qualitative interviews were conducted over a video-based conferencing platform in the United States of America with nine individuals in varying roles related to financial navigation. Thematic analysis was conducted by investigators to identify common themes using a constant comparative method. Current financial navigation training practices were found to be less structured and comprehensive than desired, largely relying on experiential "on the job" learning. Participants expressed the need for more multi-dimensional training that covers insurance, cancer treatment and associated costs, financial resources, and an emphasis on developing soft skills to navigate the sensitive topics of cancer and cancer costs. The findings contribute to the development of more standardized trainings that incorporate dissemination of crucial financial information in a compassionate manner. A web-based search was also performed to create a compilation of available financial navigation training resources.

Evidence on modifiable post-diagnosis factors influencing outcomes after intravesical Bacillus Calmette-Guérin (BCG) therapy for high-risk non-muscle-invasive bladder cancer (NMIBC) is limited. In this exploratory, feasibility-focused prospective multicenter cohort (March 2023-November 2024), BCG-naïve patients completed repeated interviewer-administered 24 h dietary recalls; prespecified food groups, selected foods, and nutrients were screened for associations with 1-year intravesical recurrence using Firth's penalized logistic regression adjusted a priori for age, sex, and total energy intake, with false discovery rate control within each exposure family. Forty-six patients were enrolled; 41 had evaluable recurrence status, including 8 recurrences (19.5%). Participants were predominantly overweight (mean body mass index (BMI) 28.4 kg/m²) and had low adherence to a Mediterranean dietary pattern (median Mediterranean Adequacy Index 2.25). No dietary exposure met the within-family false discovery rate threshold; the smallest q-value was 0.361. Nominal inverse associations were observed for leafy green vegetables (OR per 1 SD 0.385; 95% CI 0.101-0.972) and for energy-adjusted zinc (OR 0.280; 95% CI 0.069-0.802) and magnesium intakes (OR 0.260; 95% CI 0.045-0.872), but these did not remain significant after FDR adjustment. These exploratory signals warrant replication in larger, biomarker-informed cohorts incorporating dietary biomarkers and immune profiling during BCG. Given the limited sample size and low number of recurrence events, these findings are strictly hypothesis-generating and should not be interpreted as evidence of definitive protective or risk dietary factors.

Tyrosine kinase inhibitors (TKIs) added to chemotherapy have improved outcomes of adult patients with Philadelphia-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL). These improvements initially led to a larger proportion of patients realizing allogeneic stem cell transplantation (alloSCT), long considered essential for cure, but there has been a re-evaluation of alloSCT. At Princess Margaret Hospital (PM), adult patients with Ph+ B-ALL have been treated with a pediatric-inspired chemotherapy protocol with mostly imatinib. In the last two decades, we have witnessed many iterative changes in our approach. Here, we examine the outcomes of all Ph+ B-ALL patients treated at our institution from 2001 to 2019. During this time, there were two major protocol changes-omission of asparaginase in 2009 and discontinuation of routine referral for first complete remission (CR1) alloSCT from the early 2010s. Median follow-up was 41.13 months (range, 0.46-228.79). In total, 141 patients (91.56%) achieved CR1. Patient outcomes improved iteratively, with the best results seen in the final (2016-2019) cohort: no asparaginase, no routine alloSCT referral in CR1; 4-year overall survival (OS) and relapse-free survival (RFS) were 87.0% and 69.3%, respectively. The long-term OS in this patient group retained statistical significance in the multivariable analysis (p = 0.0176) when BCR::ABL1 molecular measurable residual disease (MRD) was considered.

Caudal type homeobox 2 (CDX2) is an intestine-specific transcription factor that serves as a diagnostic marker of enteric differentiation and may also reflect tumor behavior and therapeutic susceptibility. Emerging evidence suggests that CDX2 expression may predict sensitivity to fluoropyrimidine-based therapy independent of tissue of origin. We report a retrospective case series of three patients with metastatic adenocarcinoma (aggressive variant prostate, minor salivary gland, and intestinal-type sinonasal tract) exhibiting strong CDX2 nuclear expression. In all cases, tumors were refractory to or lacked established standard systemic therapy. Treatment decisions were informed by the CDX2-positive enteric phenotype, leading to the initiation of fluoropyrimidine-based regimens. Response was assessed using PET-CT and MRI. All three patients achieved marked metabolic and clinical responses, including a sustained complete metabolic response in the prostate cancer case and durable disease control in the salivary gland and sinonasal tumors. These findings highlight CDX2 as a potential biomarker requiring validation, which may identify tumors intrinsically susceptible to fluoropyrimidines regardless of anatomical origin. CDX2 immunohistochemistry is widely available and inexpensive, and may complement genomic profiling in rare malignancies or in settings where standard treatment algorithms are limited. This report is hypothesis-generating and not intended to estimate response rates or treatment efficacy.

Background: In triple-negative breast cancer (TNBC), the addition of immunotherapy has significantly improved outcomes. Immune-related adverse events (irAEs) can be accelerated in patients with pre-existing autoimmune (AI) conditions. The treatment-response standardized protocol used in clinical care raises concerns about the need for right-sizing strategies. As the use of immunotherapy expands, recognizing toxicity from recurrence and optimizing response-adapted approaches are essential to balance cure with quality of survival. Case Presentation: A 38-year-old pregnant woman with a distant history of uveitis and psoriasis was discovered to have pregnancy-associated TNBC. Postnatally, she was treated with neoadjuvant chemotherapy and pembrolizumab, followed by wire-guided left breast wide local excision and sentinel lymph node biopsy of the left axilla. After surgery, residual cancer was noted. She continued adjuvant pembrolizumab and adjuvant radiotherapy 40.05 Gy/15 fr to the breast and nodes, followed by a 13.35 Gy/5 fr boost to the tumour bed (breast). Despite a persistent residual tumour, pembrolizumab was continued as per protocol in a response-agnostic manner. At the end of one year of adjuvant pembrolizumab, she developed progressive numbness and weakness in the ipsilateral arm, initially raising suspicion for local recurrence. Comprehensive MRI and PET-CT imaging did not identify recurrent tumour or new metastatic disease. Electromyography confirmed a lower-trunk brachial plexopathy without a structural cause. An immune-mediated process was diagnosed by a process of elimination. Despite treatment with 1st-line high-dose corticosteroids and 2nd-line intravenous immunoglobulin (IVIG), improvement was limited. Therapeutic plasmapheresis led to marked functional recovery and symptom resolution 20 months later. Discussion: Four main challenges are identified: (1) the diagnostic difficulty in identifying local recurrence or radiation injury from immune-related neuropathy; (2) the emerging therapeutic role of plasmapheresis in steroid-refractory irAEs; (3) the possible inconsistencies between rare toxicities observed in clinical trials vs. clinical practice; and (4) the limitations in response in adjuvant therapy, particularly in patients with coexisting AI conditions. Conclusions: Early recognition and accurate distinction from tumour recurrence, as well as support for plasmapheresis as a potential option in steroid-refractory presentations, have been shown to improve patient survival and symptom reduction. With increasing use of immunotherapy, real-world toxicity data, predictive biomarkers, and personalized treatment strategies are urgently needed to balance cure with long-term functional outcomes.

The treatment landscape for endometrial carcinoma (EC) is undergoing a paradigm shift from traditional histopathological dualism to precision medicine grounded in the Cancer Genome Atlas (TCGA) molecular classification. The "No Specific Molecular Profile" (NSMP) subgroup, the largest molecular cohort, has emerged as a particularly promising target for endocrine-based strategies. While endocrine therapy (ET) has been a mainstay for over 60 years due to its favorable safety profile, its efficacy as monotherapy remains modest. This review provides a comprehensive overview of current endocrine strategies, including traditional agents like progestins and aromatase inhibitors, and focuses on novel combination therapies designed to overcome resistance. Recent clinical trials have demonstrated that integrating molecularly targeted agents, such as CDK4/6 and mTOR inhibitors, significantly improves clinical outcomes. Specifically, patients with TP53 wild-type status and CTNNB1 mutations exhibit exceptional responses to these combinations. Furthermore, we discuss the potential of next-generation selective estrogen receptor degraders (SERDs) and the importance of refining patient selection through robust predictive biomarkers. Driven by molecular insights, endocrine therapy is transitioning from a secondary palliative option into a definitive cornerstone of precision oncology, offering a personalized and effective treatment for patients with advanced or recurrent endometrial carcinoma.

ER-low breast cancer (1-9% ER expression) represents a biologically and clinically distinct entity at the interface between ER-positive and ER-negative disease. Although traditionally managed as hormone receptor-positive, mounting evidence indicates that ER-low tumors share molecular signatures, aggressive behavior, and chemotherapeutic responsiveness with triple-negative breast cancer. Accurate ER assessment is hindered by methodological variability and interpretative challenges, leading to potential misclassification and suboptimal treatment choices. While the benefit of endocrine therapy remains uncertain, ER-low tumors consistently show sensitivity to chemotherapy and promising responses to neoadjuvant chemo-immunotherapy, paralleling outcomes observed in triple-negative breast cancer cohorts. Emerging artificial intelligence tools, including digital pathology and multimodal deep learning, may enhance ER quantification, reduce observer variability, and enable more precise patient stratification. This review synthesizes current pathological and clinical insights into ER-low breast cancer and highlights evolving therapeutic strategies, with a forward-looking perspective on AI-driven approaches to optimize personalized treatment for this challenging subtype.

Advances in cancer therapy have markedly improved survival rates; however, long-term neurological sequelae represent a significant clinical challenge. Cancer treatment-related cognitive impairment (CRCI), commonly referred to as "chemobrain", affects a substantial proportion of cancer survivors and encompasses a broad spectrum of neuropsychiatric and cognitive symptoms, including anxiety, depression, fatigue, balance disturbances, and deficits in attention, memory, processing speed, and executive function. Increasing evidence suggests that these manifestations reflect accelerated biological aging of the brain, rather than merely transient toxic effects. This review synthesizes current clinical, molecular, and neuroimaging evidence supporting the concept of accelerated brain aging associated with multimodal cancer therapy. We summarize key molecular and cellular mechanisms including oxidative stress, neuroinflammation, blood-brain barrier dysfunction, mitochondrial impairment, cellular senescence with a senescence-associated secretory phenotype, and epigenetic remodeling that overlap with physiological brain aging hallmarks. Particular attention is given to circulating molecular biomarkers of accelerated aging, such as inflammatory mediators, senescence markers, endothelial and neuronal injury indicators, and epigenetic age acceleration, and their potential translational relevance. We discuss clinical and neuropsychological data alongside structural and functional magnetic resonance imaging findings demonstrating cortical thinning, altered gyrification, white matter microstructural changes, disrupted functional connectivity, and increased brain age estimates following cancer therapy. Framing CRCI within an accelerated brain aging paradigm may improve risk stratification, guide biomarker development, and inform personalized survivorship care.