Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype defined by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) expression. Consequently, standard hormone and HER2-targeted therapies are ineffective, necessitating reliance on chemotherapy, immunotherapy, antibody-drug conjugates (ADCs), and poly(ADP-ribose) polymerase (PARP) inhibitors for BRCA-mutated cases. TNBC exhibits rapid growth, a high risk of early recurrence, and disproportionately affects younger women, Black women, and BRCA1 mutation carriers. Standard management typically involves neoadjuvant chemotherapy followed by surgery and potential radiation. However, TNBC treatment remains challenging due to its severe biological heterogeneity, high metastatic potential, and the toxicity associated with systemic therapies. This review discusses the current understanding of TNBC biology, highlighting the urgent need for advanced diagnostics, integrated molecular subtyping, and personalized targeted therapies.

Aim:The aim of this study is to investigate the molecular and functional features underlying the clinical heterogeneity between oligometastatic (OM) and polymetastatic (PM) colon cancer.Methods:We performed a genotype-phenotype analysis in a homogeneous cohort of 127 patients with metastatic colon cancer (mCC) profiled using the same next-generation sequencing platform (TruSight Oncology® 500). OM disease was defined as the presence of one to three metastatic lesions per involved organ, involving no more than two organs overall, with all lesions measuring < 70 mm in maximum diameter and no single lesion > 25 mm. Molecular alterations, microsatellite instability (MSI), tumor mutational burden (TMB), and overall survival (OS) were analyzed. Gene Ontology (GO) enrichment and Phenolyzer network analyses were applied to explore functional differences between prognostically distinct molecular subgroups.Results:OM patients showed a striking survival advantage compared with PM patients [median OS not reached versus 29 months; hazard ratio (HR): 0.20, P < 0.0001], validating the clinical distinction between the two phenotypes. PM disease was significantly enriched for RAS mutations, whereas OM disease was associated with MSI-high status and elevated TMB. Canonical driver alterations were largely shared between groups, and Phenolyzer analysis revealed similar core oncogenic networks centered on adenomatous polyposis coli (APC), tumor protein p53 (TP53), and epidermal growth factor receptor (EGFR). In contrast, GO analysis demonstrated selective enrichment in PM tumors for molecular functions related to ATP binding, nucleotide binding, and protein kinase activity, consistent with enhanced bioenergetic demand and signaling intensity.Conclusions:These findings support refined biological stratification of mCC and the exploration of personalized, metastasis-directed strategies, potentially incorporating immunological modulation in OM disease.

This commentary discusses the FDA's drug approvals in 2025, with a particular focus on cancer therapies and the role of companion diagnostics (CDx). Cancer has emerged as the leading therapeutic area, accounting for 35% of all new drug approvals, largely driven by targeted therapies, with kinase inhibitors representing nearly half of these drugs. Many of the drugs have received orphan drug designations and/or have utilized the Accelerated Approval Program. A key finding was the widespread adoption of the drug-diagnostic co-development model, in which a CDx assay is developed along with the drug and used for patient selection in clinical trials. However, a significant challenge is the frequent lack of concurrent drug and CDx assay approvals. The absence of an analytically and clinically validated CDx assay may pose a challenge for healthcare providers in accurately identifying eligible patients, potentially delaying access to appropriate therapy. The FDA's cancer drug approvals for 2025 highlight an ongoing commitment to precision medicine, with several new targeted treatments, such as antibody-drug conjugates and kinase inhibitors, where CDx assays play an important role in identifying the appropriate patient population.

Targeted radioligand therapy (TRT) is an emerging theranostic modality in oncology. While well established in neuroendocrine and prostate cancers, its role in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) remains investigational. This systematic review summarizes current evidence evaluating TRT in lung cancer. A Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-guided systematic review of PubMed, Embase, and Scopus (2000-November 2025) was conducted. Original studies evaluating TRT in SCLC or NSCLC were included. Primary outcomes were tumor response, disease-control rate, and treatment-related toxicity. Secondary outcomes included progression-free survival, overall survival, and dosimetry. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. From 2,453 records, 15 studies were included, reporting 358 lung cancer patients, of whom 105 received TRT. Disease-control rates reached up to 78% in mixed NSCLC/SCLC cohorts. In SCLC, somatostatin receptor-targeted peptide receptor radionuclide therapy demonstrated heterogeneous disease control (0-50%), with [177Lu]Lu-labeled agents showing more favorable outcomes than [90Y]Y-based therapy. The most favorable outcomes were a median progression-free survival of 11.9 months and an overall survival of 16 months in responders. In NSCLC, fibroblast activation protein (FAP)-targeted agents such as [177Lu]Lu-FAP-2286 demonstrated partial metabolic responses, including a 44.4% response rate and 78% disease control in a mixed cohort. Severe toxicities were infrequent. TRT is a promising but experimental option for advanced lung cancer. Early efficacy signals exist for strong somatostatin receptor (SSTR)-targeted therapy in SCLC and FAP-targeted therapy in NSCLC, but evidence remains limited. Prospective trials with standardized protocols and dosimetry are needed to define TRT's role in lung cancer treatment.

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that typically arise from the pleura but may occur in various extrathoracic sites. Primary intraparenchymal pulmonary SFTs without pleural attachment are exceptionally uncommon and often pose diagnostic and therapeutic challenges. We report the case of a middle-aged female patient presenting with progressive dyspnea and a large mass in the left lower lobe on imaging. Computed tomography revealed a well-circumscribed, hypervascular mass occupying the left lower lobe. Bronchoscopic and percutaneous biopsies were nondiagnostic, and surgical resection was pursued. Intraoperatively, the tumor was found to arise from the lung parenchyma without pleural involvement. Histopathological examination demonstrated a spindle-cell neoplasm with the typical "patternless pattern," and immunohistochemistry confirmed nuclear STAT6 positivity, establishing the diagnosis of SFT. The postoperative course was uneventful apart from a transient pulmonary embolism, which was successfully treated. The patient was discharged in good condition and is under regular radiologic surveillance. SFTs of the lung are rare and often mimic more common pulmonary tumors radiologically. Histologic confirmation with STAT6 immunohistochemistry is crucial for accurate diagnosis. Complete surgical excision remains the mainstay of treatment. Given the risk of late recurrence-especially in large tumors-long-term imaging follow-up is mandatory. This case highlights the importance of considering SFT in the differential diagnosis of large pulmonary masses, the critical role of STAT6-based histopathologic confirmation, and the necessity for prolonged surveillance even after complete resection.

Intravesical Bacillus Calmette-Guérin (BCG) is the standard therapy for non-muscle invasive bladder cancer (NMIBC); however, many patients experience recurrence or progression. We examined how urinary immune signals and the urinary microbiome change across BCG and are related to outcomes. In this single-center prospective cohort study, adults with NMIBC underwent transurethral resection of bladder tumor (TURBT), followed by BCG induction. Urine was collected before TURBT, before BCG, after BCG induction, and three months later. Urine sediment mRNA (PD-L1, PD-L2, CD33, and CD204) was quantified using TaqMan ΔCt. The urinary microbiome was profiled using 16S rRNA gene sequencing, and diversity, composition, and taxon balance were evaluated using nonparametric tests, PERMANOVA, repeated-measures correlations, and mixed-effects models. We analyzed the relationship between the urinary microbiome and prognosis. Twenty-three patients were analyzed; ten recurrences, eight progressions, and three deaths were observed. Relative to baseline, CD33 increased after BCG and after three months; PD-L2 increased immediately after BCG and returned to baseline by three months; PD-L1 and CD204 increased after BCG. Shannon alpha-diversity was unchanged, but total read count was higher at three months, with stable beta-diversity and dispersion. Higher PD-L1 expression was associated with lower Actinobacteria abundance in the bladder cancer microenvironment. A higher post-BCG Firmicutes/Bacteroidetes ratio was associated with worse prognosis, with the clearest signal for progression-free survival (PFS) observed in the univariate Cox models. Higher post-BCG Corynebacterium and Enterobacteriaceae abundance was associated with better PFS. BCG was associated with higher urinary PD-L1/PD-L2 and myeloid marker transcripts, while overall community structure remained stable. These exploratory data support that pre-BCG microbial features may be related to early response, and post-BCG profiles may reflect durability and survival. Urine immune-microbiome profiling could be a feasible, noninvasive adjunct for monitoring and risk stratification in NMIBC.

Aim:Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options and poor survival outcomes. Prognostic models developed in Western cohorts rarely assess algorithmic fairness. This study aimed to develop and internally validate a clinically interpretable Cox survival model for TNBC using baseline diagnostic variables and to evaluate its fairness according to ISO/IEC TR 24027:2021 guidelines in a Middle East and North Africa (MENA) cohort.Methods:A total of 138 TNBC patients were included after merging two institutional datasets and removing variables with > 25% missingness. Baseline features comprised age, tumor size, lymph node involvement, tumor grade, Ki-67, type of surgery, metastasis at diagnosis, chemotherapy, and radiotherapy. A Cox proportional hazards (CoxPH) model with six clinically established predictors was fitted to reduce overfitting. Model performance was assessed through five-fold stratified cross-validation using Harrell’s concordance index (C-index), receiver operating characteristic area under the curve (AUROC), and calibration curves. Fairness was evaluated using demographic parity, equality of opportunity, predictive equality, and equalized odds metrics following ISO/IEC TR 24027:2021.Results:During follow-up, 34 patients (24.6%) died. Metastasis at diagnosis, high tumor grade, and radical mastectomy were significantly associated with mortality. The CoxPH model achieved a C-index of 0.80 [SE = 0.04; 95% confidence interval (CI): 0.72–0.87] and an AUROC of 0.81 (95% CI: 0.72–0.90). Calibration plots showed strong agreement between predicted and observed survival probabilities, with a modest overall bias of –8.8%. Fairness assessment revealed small but notable disparities in false-positive rates across age groups and surgical categories, while lymph node status and other variables showed no significant bias.Conclusions:This study presents a robust and fairness-aware survival prediction model for TNBC using routinely available clinical features. The model demonstrates strong discrimination, good calibration, and quantifiable fairness across patient subgroups, offering a clinically interpretable and ethically aligned tool to support TNBC risk stratification and decision-making in the MENA region.

Breast cancer is a leading cause of cancer death in women worldwide. One of the major causes of death from breast cancer is metastatic disease, which results from the malignant cells invading and migrating through blood vessels to distant sites. Several studies have shown that metastasis is facilitated by haemostatic proteins. Breast cancer is characterized by a haemostatic imbalance, which is tilted more to a procoagulant state with resultant thrombotic complications. These elements that are involved in thrombosis also play key roles in different aspects of breast cancer growth, including cancer proliferation and progression, cancer survival, angiogenesis, and metastasis. Some of these elements include platelets, endothelial cells, coagulation factors, and fibrinolytic proteins. There is a close relationship between cancer and many of the haemostatic elements. They are usually increased in metastatic breast cancer and have found use as predictive and prognostic markers. Some have been validated in breast cancer. Due to their seemingly active roles in breast cancer progression, some of the haemostatic proteins are being developed as diagnostic tools in the management of breast cancer. They are equally seen as potential targets for the development of novel therapies in breast cancer or repurposing drugs in current use for the same gain. This review highlights the role haemostatic proteins play in breast cancer progression, and their diagnostic and therapeutic relevance.

Docetaxel is a cornerstone chemotherapy for metastatic hormone-sensitive and castration-resistant prostate cancer. Although the standard triweekly regimen is widely used, weekly and biweekly schedules are often employed to improve tolerability, particularly in elderly or frail patients. The comparative efficacy and safety of these dosing strategies remain unclear. This study aimed to systematically compare weekly, biweekly, and triweekly docetaxel regimens using a network meta-analysis. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to February 2025. Randomized controlled trials and observational retrospective studies comparing weekly, biweekly, and triweekly docetaxel regimens were included. Outcomes assessed were prostate-specific antigen (PSA) response rate, time to treatment failure or progression, and adverse events. A frequentist random-effects network meta-analysis was conducted using R software. Eleven studies involving 1,238 patients were included. PSA response rates did not differ significantly among regimens; triweekly docetaxel showed a numerically lower response compared with weekly dosing (RR = 0.79, 95% CI 0.52-1.22; I2 = 41.1%). Time to treatment failure was significantly longer with triweekly dosing compared with weekly dosing (mean difference = 10.91 months, 95% CI 6.94-14.87; I2 = 96.8%). Biweekly and triweekly regimens were associated with significantly higher hepatotoxicity compared with weekly dosing (RR = 3.71 and RR = 3.21, respectively; I2 = 0%). Vomiting was more frequent with triweekly docetaxel (RR = 2.47, 95% CI 1.31-4.63). No significant differences were observed for overall adverse events, hematologic toxicity, neuropathy, fatigue, febrile neutropenia, nausea, anorexia, or diarrhea. Docetaxel dosing schedules show comparable PSA response rates. Triweekly dosing prolongs time to treatment failure but is associated with greater toxicity, whereas weekly dosing offers better tolerability. Treatment decisions should balance efficacy and safety based on individual patient characteristics.

Acquired middle-ear cholesteatoma is a histologically benign keratinizing squamous epithelial lesion that paradoxically exhibits locally destructive, recurrent, and invasive behavior, often resulting in ossicular erosion, hearing loss, labyrinthine fistula, and, rarely, intracranial complications. Surgical excision remains the primary management strategy; however, recurrence is common due to persistent microenvironmental drivers. Recent mechanistic studies-including single-cell transcriptomics, spatial proteomics, and epigenetic profiling-reveal a multifactorial pathogenesis orchestrated by chronic inflammation, proteolytic extracellular-matrix remodeling, osteoclast activation via RANKL and activin A, epithelial plasticity with partial epithelial-to-mesenchymal transition (EMT), and a dysbiotic, biofilm-forming microbiome. Emerging evidence further implicates oxidative stress, RNA and epigenetic modifications, miRNA dysregulation, and immune cell infiltration as central modulators of lesion chronicity and bone resorption. Collectively, these processes establish a self-sustaining pro-osteolytic microenvironment that drives bone erosion and postoperative recurrence. Cholesteatoma recapitulates several features of malignant lesions-hyperproliferation, local invasion, and stromal/immune cell recruitment-yet remains fundamentally benign, lacking metastatic potential and genomic instability. Its aggression is ecological rather than genetic, highlighting the potential for microenvironment-directed, precision-based strategies. Adjunctive approaches may include local delivery of modulatory agents, targeted interference with inflammatory, proteolytic, osteoclastogenic, and microbial axes, and biomarker-guided patient stratification. Preclinical and early-phase experimental studies assessing target engagement, radiologic stabilization, and molecular surrogates of efficacy could inform safer, mechanism-driven interventions that complement surgery, reduce recurrence, and preserve hearing. Integrating molecular pathobiology with clinical strategy positions cholesteatoma as a model for benign yet locally aggressive, microenvironment-driven disease, providing a roadmap for translational therapies with direct relevance to surgical practice.