搜索结果：Targeted oncology

Bahrain reports the highest age-standardized cancer incidence among Gulf Cooperation Council (GCC) countries, but its oncology research output has not been comprehensively mapped. We profiled four decades of Bahrain-linked cancer publications to describe growth, contributors, collaboration, impact, and gaps. We searched Scopus and PubMed from inception to December 2024 using cancer-related terms combined with "Bahrain". We included articles, reviews, editorials, letters, conference papers, and book chapters. After deduplication, screening, and manual supplementation, 502 publications were analyzed by year, document type, journal quartile, SCImago Journal Rank (SJR), Bahraini authorship and first-author affiliation, geographic scope, study design, citations, and cancer site grouped using the ICD-O (3rd edition). The first indexed paper appeared in 1981. Output was low until 2010, then increased sharply; 77.7% of publications appeared from 2011 to 2024, peaking at 66 papers in 2024. Articles accounted for 69.3% of the outputs, and reviews accounted for 21.7%, with greater diversity after 2010. The Bahrain Medical Bulletin was the most common outlet (20.2%). Salmaniya Medical Complex led in first-author output, followed by Arabian Gulf University and King Hamad University Hospital. Bahraini first authorship was observed in 66.7% of papers, and most studies were conducted exclusively in Bahrain (65.3%), although the proportion of global collaborations increased to 17.0% from 2021 to 2024. Descriptive designs predominated (57%, including 25.5% case reports), whereas analytic studies were uncommon (4.3%). Breast cancer was the most studied site-specific cancer (23.3%), followed by digestive organ cancers (11.4%); 27.1% of the papers addressed "unspecified" cancer. Respiratory and intrathoracic cancers remain persistently underrepresented despite a high mortality burden. Journal quality improved after 2010, reflected by increasing Q1/Q2 representation and higher SJR distributions. The citation peaks from 2014 to 2018 were driven by highly cited multinational collaborative publications. Bahrain's oncology research output has increased more than 30-fold over four decades, with expanding institutional participation and increasing international collaboration. Persistent reliance on descriptive designs and gaps in high-burden cancers-especially lung cancer-highlights priorities for capacity building, targeted funding, and a nationally aligned oncology research agenda for policy action.

Curcumin, a naturally occurring polyphenolic compound isolated from Curcuma longa, has been extensively studied for its nutritional, antioxidant, anti-inflammatory, anticancer, and neuroprotective properties. While traditionally recognized as a dietary bioactive with therapeutic relevance, recent advances in nanotechnology, molecular imaging, and targeted drug delivery have positioned curcumin as a promising theranostics agent. Theranostics integrates diagnostic imaging and therapy within a single platform, enabling real-time visualization of disease processes alongside targeted intervention. This review critically examines the emerging role of curcumin in imaging-guided therapeutics, with particular emphasis on oncology and neurodegenerative disorders. Curcumin's intrinsic fluorescence, affinity for pathological proteins, and modulatory effects on key molecular pathways underpin its potential as both an imaging probe and a therapeutic molecule. Key challenges related to poor aqueous solubility, rapid metabolism, and limited bioavailability are discussed, along with innovative delivery strategies such as nanoparticles, liposomes, radiolabelled conjugates, and stimulus-responsive systems designed to enhance clinical applicability. By bridging its established nutritional significance with advanced theranostics applications, curcumin exemplifies the translational potential of plant-derived bioactive in precision medicine. This review highlights current progress, limitations, and future perspectives, positioning curcumin as a model phytoconstituent for the development of integrated diagnostic and therapeutic platforms in complex chronic diseases.

Molecular hydrogen (H2) therapy has emerged as a promising adjunctive strategy in oncology, primarily attributed to its selective antioxidant, anti-inflammatory, and cytoprotective properties. Advances have been driven by the integration of mechanistic studies on H2-mediated redox regulation, immunoregulation, and cytoprotective effects with rapid developments in nanotechnology and catalysis. Nevertheless, the clinical translation of H2 therapy remains constrained by the present physicochemical limitations, including low solubility, non-targeted diffusion, the incomplete understanding of therapeutic mechanisms, etc. This review summarizes recent progress in molecular H2 research, spanning from fundamental mechanisms in cancer biology, the role in adjuvant therapy, to the development of innovative catalytic delivery systems, such as stimuli-responsive materials and hydrogenases. We outline the pertinent challenges and future directions, emphasizing the need for mechanistic elucidation and robust clinical validation to integrate hydrogen therapy into precision oncology paradigms.

The gut microbiome is a fundamental determinant of gastrointestinal physiology. It is essential in maintaining host homeostasis while also implicated in cancer pathogenesis and alteration in physiological response to surgical stress. This narrative review evaluates the microbiome's mechanistic role in surgical oncology, assessing it as a biomarker for risk stratification and an emerging therapeutic target. The current literature was synthesized to examine microbial impacts on tumourigenesis and perioperative surgical outcomes across the lower and upper gastrointestinal tracts (including the gut-lung axis), the hepatopancreatobiliary system, and extra-abdominal malignancies (breast cancer and melanoma). Dysbiotic microbial signatures, termed the oncobiome, actively drive tumour progression and immune evasion. Perioperative interventions induce acute microbial shifts linked to serious complications such as anastomotic leaks and pneumonia. Clinically, targeted modulation yields significant benefits as demonstrated by: perioperative synbiotics reducing infectious complications by 45% in colorectal surgery and 64% in major liver surgery. Furthermore, preoperative oral care reduces post-esophagectomy pneumonia by up to 50%, while Helicobacter pylori eradication halves metachronous gastric cancer risk. However, a detrimental "antibiotic paradox" exists in melanoma, where pre-treatment antibiotic exposure severely impairs immune checkpoint inhibitor efficacy. Conversely, faecal microbiota transplantation can reverse this immunotherapy resistance, achieving up to 80% response rates in trials. The microbiome is a critical, modifiable determinant of both short-term surgical recovery and long-term oncologic survival. Future surgical oncology practice will need to integrate precision surgical microbiome-mediated biotherapeutics to optimise outcomes in multidisciplinary cancer care.

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy often detected at an advanced stage with limited effective treatment options beyond first-line chemotherapy. The liver is a common site of metastasis, and patients frequently present with substantial hepatic disease burden that precludes complete resection. Locoregional therapies, including hepatic artery infusion pump (HAIP) delivery of floxuridine, have not been thoroughly evaluated for treatment of ACC liver metastasis, likely due to its rare incidence and highly aggressive nature. PDS01ADC (previously referred to as NHS-IL12) is a novel antibody-drug conjugate designed to deliver the immunomodulatory cytokine interleukin-12 to areas of tumor necrosis and modulate the tumor microenvironment to support immune surveillance and cytotoxic tumor responses. Combination of PDS01ADC with HAIP therapy (HAIP-delivered floxuridine plus systemic chemotherapy) was recently found to be feasible for clinical evaluation by an interim analysis in patients with colorectal liver metastases. Patients who received PDS01ADC with HAIP therapy had extended overall survival compared to patients who received HAIP therapy alone in a nonrandomized prior sequential study. We discuss herein the rationale and initiation of a new clinical trial arm to evaluate HAIP therapy with PDS01ADC for patients with ACC liver metastasis who have failed standard of care therapy. Patients with unresectable ACC liver metastasis and either resectable or no progressive extrahepatic disease will receive combination therapy including HAIP floxuridine and subcutaneous injection of PDS01ADC administered concurrently with systemic gemcitabine and oxaliplatin in 28-day cycles. The primary outcome measured is overall response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. Secondary outcomes measured in this study include intrahepatic and extrahepatic progression-free survival, overall survival, and safety of PDS01ADC combination therapy with HAIP-delivered floxuridine. For select patients with ACC liver metastasis, HAIP therapy with PDS01ADC may improve disease control and thereby prolong survival. Study ID NCT05286814 version 2026-05-04; https://clinicaltrials.gov/study/NCT05286814. Adrenocortical carcinoma (ACC) is a highly lethal malignancy with few treatment options, especially in the setting of distant metastases. The liver is a common site of disease spread, with numerous metastases frequently limiting locoregional therapy options that specifically target the liver. This study protocol describes the rationale for a new clinical trial arm for patients with ACC liver metastasis, evaluating high dose chemotherapy (HAIP floxuridine) delivered directly to the liver in combination with a targeted immunotherapy (PDS01ADC) designed to enhance immune responses within the tumor microenvironment. Combined with systemic chemotherapy (gemcitabine plus oxaliplatin), this approach leverages both liver-targeted and systemic (whole body) mechanisms to overcome treatment resistance and reduce tumor burden. The rationale to test this therapy for patients with ACC liver metastasis includes promising case studies using HAIP floxuridine for ACC liver metastasis as well as recent clinical data evaluating the safety and early efficacy of HAIP floxuridine combined with PDS01ADC in patients with colorectal liver metastases. It is important to expand this treatment evaluation to patients with ACC liver metastasis as this disease is highly aggressive with few options for effective treatment.

Interleukin-5 (IL-5) is a central regulator of eosinophil differentiation, maturation, survival, activation, and mobilization, and it contributes to eosinophil recruitment to inflamed tissues. These biological functions have made the IL-5/IL-5 receptor alpha (IL-5Rα) pathway a key therapeutic target in eosinophil-associated diseases. Four biologics currently target this pathway in clinical practice: mepolizumab, reslizumab, and depemokimab bind soluble IL-5, whereas benralizumab targets IL-5Rα and induces antibody-dependent cellular cytotoxicity. Clinical development has been successful in severe eosinophilic asthma (SEA), where targeting the IL-5/IL-5Rα pathway reduces exacerbation risk and can lower the need for long-term oral corticosteroid use. The therapeutic scope has since expanded to chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatosis with polyangiitis (EGPA), and idiopathic hypereosinophilic syndrome (iHES). Mepolizumab has shown efficacy across these eosinophilia-associated diseases, reducing asthma exacerbations, nasal polyp burden, EGPA relapse activity, HES flares, and eosinophils in peripheral blood. Mepolizumab is approved by both FDA and EMA for SEA, CRSwNP, EGPA, and HES. Reslizumab improves exacerbation rates and lung function in SEA and is approved by FDA and EMA for this indication. Benralizumab produces rapid and near-complete blood and tissue eosinophil depletion, reduces exacerbation rates and oral corticosteroid use in SEA, and has demonstrated sustained remissions and corticosteroid-sparing efficacy in EGPA; it is approved by FDA and EMA for SEA and EGPA. Depemokimab extends IL-5 inhibition through a long-acting, twice-yearly dosing strategy, reduces exacerbation rates in SEA, and improves nasal polyp burden in CRSwNP; it is approved by FDA and EMA for SEA and by EMA for CRSwNP. Safety data from randomized trials, extension studies, real-world cohorts, and meta-analyses are generally reassuring, with most adverse events being mild to moderate and no consistent major safety signal. This review synthesizes current understanding of IL-5 biology, critically evaluates the clinical trial evidence for IL-5/IL-5Ra-targeted biologics across major eosinophilia-associated diseases, and highlights remaining evidence gaps and future directions.

Meningiomas are the most common primary intracranial tumor in adults. Beyond surgery and radiation, no standard of care therapy exists. Meningiomas overexpress somatostatin receptor 2 (SSTR2), providing the rationale for somatostatin analogue-based therapies, including octreotide. The addition of everolimus, a mammalian target of rapamycin inhibitor, to octreotide marginally improves the 6-month progression-free survival (PFS) rate. For this reason, novel therapies have emerged for the treatment of refractory meningiomas, including somatostatin receptor targeted radionuclide therapy. However, preliminary results with refractory meningiomas treated with single agent 177Lu-DOTATATE, a β-emitting peptide receptor radionuclide therapy (PRRT), demonstrated outcomes comparable to those observed with combination octreotide and everolimus. In contrast, in neuroendocrine tumors (NETs), octreotide combined with PRRT has shown significant prolongation of PFS compared to high-dose octreotide alone. The final analysis of the NETTER-1 trial also yielded a trend towards an improvement in median overall survival, supporting the FDA approval of 177Lu-DOTATATE in 2018 for use in NETs. We present the first case of a refractory meningioma patient treated with combination PRRT and octreotide in a 66-year-old male who received 177Lu-DOTATATE 7.4 GBq (200 mCi) and intramuscular long-acting octreotide 40 mg every 8 weeks for four cycles followed by a single cycle of octreotide 40 mg monotherapy. Treatment was discontinued due to his unfortunate death from non-treatment related causes, occurring 2.5 months from his final octreotide dose. A 7-week post-treatment MRI brain demonstrated stable disease with 11.5% reduction per RANO-Meningioma and a 2.6% reduction per RECIST 1.1 criteria. Combined PRRT and octreotide represents a promising therapeutic strategy for patients with refractory meningioma.

Anaplastic lymphoma kinase-targeted tyrosine kinase inhibitors (ALK-TKIs) have revolutionized the treatment of non-small-cell lung cancer (NSCLC). However, several key issues remain unresolved. Specifically, the impact of prior chemotherapy on ALK-TKI efficacy is unclear, the impact of MET overexpression on ALK-TKI efficacy remains unclear, and the dynamic changes in programmed death ligand 1 (PD-L1) expression during the development of TKI resistance are not fully understood. This study aimed to evaluate the efficacy of ALK-TKIs across different treatment lines, analyze the impact of MET expression on treatment outcomes, and investigate changes in PD-L1 expression before and after the development of resistance. Retrospective cohort study. A retrospective analysis was conducted on 259 patients with ALK-positive NSCLC treated at Zhejiang Cancer Hospital between 2011 and 2022 to compare the efficacy of ALK-TKIs administered as first-line therapy versus after chemotherapy. Immunohistochemical staining was used to assess MET and PD-L1 expression. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. Crizotinib showed no significant difference in progression-free survival (PFS) or overall survival (OS) between first-line and post-chemotherapy use (PFS: p = 0.803; OS: p = 0.761). For second-generation ALK-TKIs, first-line treatment had numerically longer PFS compared to post-chemotherapy (alectinib: 41 vs 24 months; ceritinib: 30 vs 8 months), but these differences were not statistically significant after adjustment (p = 0.120 and 0.284, respectively). OS did not differ significantly between the two treatment sequences for either drug. Notably, among patients treated with alectinib, those with MET overexpression had significantly shorter PFS (12 vs 42 months; p = 0.011) and OS (41 months vs not reached; p = 0.001) compared with MET-negative patients. There was no significant change in PD-L1 expression following resistance (p = 0.248). ALK-TKIs have shown a tendency to improve patient survival in both first-line and post-chemotherapy settings. Among patients treated with alectinib, there appears to be a trend toward shorter PFS and OS in those with MET overexpression. In a limited number of matched samples, PD-L1 expression did not change significantly after TKI resistance, although a slight increase was observed.

Triple-negative breast cancer demonstrated high metastasis and mortality rates in female populations. Emerging data on effective targeting and specific internalization of chemotherapeutic agents, using modified exosomes, decreased the therapeutic dosage of anti-cancer drugs in cancer cells. Herein, we developed modified exosomes by surface decoration using the Fusion protein of Respiratory Syncytial Virus (F-protein of RSV) through Click-chemistry techniques, and Dox-loaded via sonication strategy. Then, the viability and metastatic behaviors of MDA-MB-231 cells were monitored in the presence of different groups, including Dox, Exosomes (Exo), Exosomes loaded with Dox (Exo@Dox), and F-protein coupled Exosome groups (Exo-F) and (Exo-F@Dox). In vitro and in vivo results verified that the F-protein coupled exosome, as a modified natural nanoplatform, possessed a biocompatible nature in blood circulation and crossing of blood barriers. After exposure to tumoral temperature (40 &#xb0;C) and lysosomal PH (5.5) demonstrate amplified Dox release (around 60% at 8 h). Also, in vitro uptake results confirmed a significant increase in Exo-F internalization compared to the Exo group in MDA-MB-231 cells (P<0.0001). Correspondingly, the IC50 value of Exo-F@Dox versus free Dox showed a significant reduction (24-fold more potent) (P<0.0001). Interestingly, Dox-free modified Exo (Exo-F) showed appreciable cytotoxicity (IC50 of about 0.1 &#xb5;g /mL for exosomal protein concentration) (P&#x2c2;0.0001). Also, migration assay results confirmed a considerable decrease in the migrated population of MDA-MB-231 cells (10%) compared to the control group, following exposure to modified exosomes. Interestingly, an in vivo study in tumor-bearing Balb/c mice demonstrated a significantly decreased tumor size in the Exo-F groups compared to other formulations. In summary, F-protein modified exosomes exhibited superior anticancer efficacy by improving tumor-specific targeting, ensuring precise delivery of chemotherapeutic agents, facilitating efficient drug release, and allowing for lower therapeutic dosages.

National clinical guidelines recommend biomarker testing to identify actionable alterations across cancers, supporting personalized treatment. This retrospective database study characterized biomarker testing patterns among adult patients newly diagnosed with metastatic non-small cell lung cancer (NSCLC), prostate cancer, or bladder cancer (January 2018-December 2022), receiving care within a large regional community oncology network in the West South-Central United States. Of 18 491 patients with NSCLC, 20 810 with prostate cancer, and 4120 with bladder cancer, 7383 (40%), 4985 (24%), and 888 (22%), respectively, had metastatic disease. For these metastatic subgroups, biomarker testing rates were 80% (NSCLC), 34% (prostate), and 42% (bladder). Median time from disease diagnosis to first test order was 10&#x2009;days (NSCLC), 98&#x2009;days (prostate), and 23&#x2009;days (bladder), with differences observed across racial and ethnic groups. Among tested patients, actionable mutations were identified in 29% (NSCLC), 25% (prostate), and 14% (bladder) of patients, and targeted therapy was received by 54%, 15%, and 38% of these patients, respectively. Among patients who initiated treatment prior to receipt of test results, 72% (NSCLC), 12% (prostate), and 30% (bladder) subsequently switched to targeted therapy following a positive result. Testing rates increased between 2018 and 2022 for all cohorts; result turnaround times improved in prostate and bladder cancers. Biomarker testing was highest in metastatic NSCLC and lower in prostate and bladder cancer in this community oncology setting. Despite improvements over time, gaps remain in timely testing and use of targeted therapies, highlighting opportunities to optimize precision oncology implementation.

CLDN18.2, a tight junction protein aberrantly overexpressed in gastric, pancreatic, and other cancers but minimally expressed in normal tissues, is a promising target for antibody-drug conjugate (ADC)-based therapies. This study describes the development and preclinical characterization of h1D6-ADC-5, a novel ADC composed of a proprietary humanized anti-CLDN18.2 monoclonal antibody (h1D6) and the cytotoxic payload DUO-5, conjugated via site-specific technology. h1D6 was generated by immunizing CLDN18.2 knockout mice followed by humanization; it exhibited high specificity for CLDN18.2 (no cross-reactivity with CLDN18.1) and improved binding affinity and in vivo efficacy vs. existing antibodies (e.g., IMAB362). Using C-Lock site-directed conjugation, h1D6 was linked to DUO-5 (a tubulin polymerization inhibitor) to yield h1D6-ADC-5 with a controlled average drug-to-antibody ratio of 4.3. In vitro, h1D6-ADC-5 selectively bound CLDN18.2-positive cells (AGS-CLDN18.2, NUGC4), were efficiently internalized, and induced apoptosis by downregulating anti-apoptotic proteins and upregulating pro-apoptotic markers. It also exerted a "bystander effect," killing adjacent CLDN18.2-negative cells via released DUO-5. In vivo, 89Zr-labeled h1D6-ADC-5 showed prolonged tumor accumulation in CLDN18.2-positive xenograft, with significant tumor regression (nearly complete regression at 10&#xa0;mg/kg) while no overt toxicity was observed based on body weight and histology. These preclinical data demonstrate that h1D6-ADC-5 is a promising candidate for treating CLDN18.2-positive cancers.

Determining an optimal treatment strategy after tyrosine kinase inhibitor (TKI) failure remains challenging in oncogene-driven non-small cell lung cancer (NSCLC). We aimed to evaluate and compare the efficacy and safety of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) versus pemetrexed plus carboplatin or cisplatin (PC) in patients with progressive NSCLC harboring EGFR, ALK, or ROS1 alterations after TKI failure. Multicenter retrospective study. We analyzed 114 patients with NSCLC treated with either ABCP (n&#x2009;=&#x2009;48) or PC (n&#x2009;=&#x2009;66) post-TKI failure between November 2016 and July 2023. Treatment response, progression-free survival (PFS), overall survival (OS), and safety profiles were assessed. Among 106 evaluable participants, the ABCP arm demonstrated a higher response rate (50.0%) than the PC arm (35.0%). During the median follow-up of 29.9&#x2009;months, PFS was significantly prolonged in the ABCP arm compared with that in the PC arm (7.3 vs 3.0&#x2009;months, respectively; hazard ratio (HR) 0.643; p&#x2009;=&#x2009;0.026), whereas OS showed no significant difference (p&#x2009;=&#x2009;0.165). Subgroup analysis revealed notable improvements in PFS (7.2 vs 2.1&#x2009;months, HR 0.235; p&#x2009;<&#x2009;0.001) and OS (11.0 vs 4.1&#x2009;months, HR 0.418; p&#x2009;=&#x2009;0.001) in patients with three or more metastatic sites. ABCP significantly improved PFS compared with PC in patients with NSCLC that progressed despite prior TKI therapy. An OS benefit was observed in patients with three or more metastatic sites. Combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) improves progression-free survival compared to pemetrexed and carboplatin (PC) in patients with non-small cell lung cancer after targeted therapy fails. Why was this study done? Many patients with non-small cell lung cancer (NSCLC) have specific genetic alterations (mutations like EGFR, ALK, or ROS1). The standard first line treatment for this population is targeted therapy. However, many patients discontinue these drugs because cancer eventually gains resistance to the target therapy. There are unmet needs for patients whose target therapies are exhausted since there are no guideline for subsequent treatment. What did the researchers do? This study compared the effectiveness of two different chemotherapy combinations for patients whose cancer grew after taking targeted pills. The researchers retrospectively analyzed data from 114 patients treated between 2016 and 2023. The patients received either: ABCP: A four-drug combination of atezolizumab (immunotherapy), bevacizumab (anti-VEGF therapy), paclitaxel, and carboplatin (cytotoxic chemotherapy) PC: A two-drug cytotoxic chemotherapy regimen (pemetrexed plus carboplatin). What were the results? The study found that the four-drug combination (ABCP) was more effective at controlling the cancer: Delayed Growth: On average, patients on ABCP went 7.3&#x2009;months before their cancer started growing again, compared to only 3.0&#x2009;months for those on PC. Tumor Shrinkage: Tumors shrank in 50% of patients taking ABCP, compared to 35% of patients taking PC. Survival: While the overall survival time was similar for both groups, patients with more widespread cancer (spread to 3 or more sites) lived significantly longer if they received the ABCP treatment. What do these findings mean? For patients with NSCLC whose targeted therapy has been exhausted, using the ABCP combination appears to keep the cancer under control significantly longer than PC. It may be a particularly good option for patients whose cancer has spread to multiple parts of the body.

Renal cell carcinoma (RCC) is increasingly managed with a broad range of systemic and local therapies, creating new challenges for imaging-based response assessment in metastatic disease. While conventional size-based criteria such as RECIST v1.1 remain widely used, they incompletely capture the diverse morphologic and functional changes induced by modern treatment. Targeted therapies, including vascular endothelial growth factor receptor tyrosine kinase inhibitors and other pathway-directed agents, may produce necrosis, devascularisation, and prolonged disease stability without substantial tumour shrinkage. Immune checkpoint inhibitors introduce additional atypical response patterns, including pseudoprogression, mixed response, and rarely hyperprogression, which can complicate early interpretation of surveillance imaging. Combination regimens may demonstrate features of both targeted and immune-mediated response. In parallel, stereotactic body radiotherapy has emerged as an important treatment for oligometastatic and oligoprogressive RCC, with imaging appearances that may include lesion shrinkage, stability, or transient enlargement following treatment. This review summarises the current treatment landscape for metastatic RCC and the imaging manifestations of response across chemotherapy, targeted therapy, immunotherapy, combination systemic therapy, and stereotactic radiotherapy. It discusses the strengths and limitations of conventional and modified response criteria, including RECIST v1.1, iRECIST, attenuation-based CT criteria, and morphology-based approaches. The review also highlights the evolving role of functional and novel imaging techniques, including diffusion-weighted whole-body MRI, dual-energy and spectral CT, and PET/CT, as potential tools for improving response assessment beyond size alone. In addition, key imaging features of treatment-related toxicity are reviewed. Familiarity with these response patterns and complications is essential for radiologists involved in the care of patients with metastatic RCC, particularly as treatment strategies become increasingly multimodal and biologically complex.

Thiocolchicoside is a colchicoside compound that is partly synthetic and is most known for its characteristics of centrally acting muscle relaxants. It has been widely used in the management of musculoskeletal disorders due to its ability to modulate inhibitory neurotransmission. Recent research has shown potential in additional therapeutic domains, such as antimicrobial, anticancer, and anti-inflammatory. The objective of this review is to provide a comprehensive overview of the chemical profile of thiocolchicoside, including how it works, pharmacokinetics, traditional and novel therapeutic uses, safety concerns, and recent advances in drug delivery systems. Special emphasis is given to its emerging roles in oncology and infectious disease management. Relevant literature was collected from PubMed, Scopus, Google Scholar, and other scientific databases. Preclinical and clinical studies, review articles, case reports, and regulatory documents related to thiocolchicoside were reviewed to extract updated and critical information. Thiocolchicoside exerts its effects by acting as a competitive antagonist on gamma-aminobutyric acid type A (GABA-A) and glycine receptors, leading to muscle relaxation without strong sedation. Several preclinical studies suggest anti-inflammatory, analgesic, antimicrobial, and cytotoxic potential. Recent innovations include nanogel-based formulations and other targeted delivery systems to enhance bioavailability and reduce systemic toxicity. However, concerns remain regarding its genotoxicity and myelosuppressive effects, particularly at higher doses or with prolonged use. Thiocolchicoside remains a valuable agent in pain and spasm management, but its expanding therapeutic spectrum suggests opportunities for drug repurposing, especially in oncology and infectious disease. Future research ought to concentrate on safety optimization, chronic toxicity studies, and the development of novel delivery platforms to maximize therapeutic efficacy while minimizing risks.

The COVID-19 pandemic caused significant disruptions in oncology services worldwide. Breast cancer care depends on timely and coordinated treatment pathways. This review assessed changes in systemic anti-cancer therapy, including chemotherapy, endocrine therapy, targeted therapy, and immunotherapy. Secondary outcomes included treatment delays, short-term mortality, and hospital admissions. We conducted a systematic review and meta-analysis following PRISMA guidelines. The protocol was registered with PROSPERO (CRD42024542702). We searched PubMed, Scopus, Web of Science, and CINAHL for studies published between March 2020 and August 2024. We included original studies comparing adult breast cancer patients treated before and during the pandemic. Patients of any stage and sex were eligible. We assessed risk of bias and used a random-effects model to present pooled proportions and odds ratios (ORs) with 95% confidence intervals (CIs). Forty-eight studies were included in the review, and 35 in the meta-analysis. Chemotherapy use increased from 35% before the pandemic to 42% during the pandemic. This rise was driven by an increase in neoadjuvant chemotherapy, from 18% to 22%, while adjuvant chemotherapy remained stable. Endocrine therapy increased from 35% to 42%. Neoadjuvant endocrine therapy rose from 2% to 10%, whereas adjuvant endocrine therapy declined from 46% to 43%. Targeted therapy and immunotherapy showed minimal change. The pooled OR for short-term mortality was 0.81 (95% CI: 0.56-1.15). Hospital admission estimates showed wide confidence intervals, reflecting heterogeneity. The pandemic led to notable shifts in systemic treatment patterns, particularly an increase in the use of neoadjuvant strategies. Short-term mortality did not significantly differ between periods. The study findings should be interpreted with caution due to variability in studies. Health systems require robust pharmaceutical policies and resilient triage frameworks to ensure continuity of cancer treatment during future crises.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma in older adults. Treatment in this population remains challenging due to heightened genetic heterogeneity and reduced physiological reserve, which increase susceptibility to both treatment-related toxicity and the risk of undertreatment. Comprehensive geriatric assessment is essential to categorize patients as fit, unfit, or frail, enabling individualized therapeutic strategies. Fit patients benefit from standard R-CHOP or Pola-R-CHP regimens, while unfit patients are suitable for dose-reduced regimens. Anthracycline-containing therapy is recommended when feasible; alternatives such as etoposide or gemcitabine may be used when anthracyclines are contraindicated. Frail patients lack standardized treatment protocols, presenting a significant clinical dilemma; however, advances in geriatric assessment tools and novel therapies are expected to shift the management paradigms from purely palliative care to curative&#x2011;intent strategies. Current geriatric assessment tools have limitations, and the distinction between unfit and frail remains fluid. Dynamic fitness assessment and pre-phase treatment strategies may enable some patients to "improve" to a higher fitness level. Emerging evidence supports the efficacy of novel targeted agents, including small-molecule inhibitors, bispecific antibodies, and antibody-drug conjugates, which are reshaping first-line treatment paradigms. Nevertheless, their implementation in community settings faces substantial practical barriers, such as the need for cytokine release syndrome monitoring, caregiver burden, financial toxicity, and adherence challenges. This review provides a comprehensive overview of current strategies and emerging directions for managing older adults with DLBCL. Personalizing treatment for older adults with diffuse large B-cell lymphoma Treating diffuse large B-cell lymphoma (DLBCL) in older adults is challenging. Many older patients often have other health issues and lower physical reserves, making it harder to tolerate standard chemotherapy. This review discusses how treatment strategies are evolving to better meet the needs of this population. A key step is tailoring treatment based on a patient&#x2019;s overall health and fitness level, not just their age. Through a geriatric assessment, doctors can better understand how well a patient may handle treatment, helping to determine whether a more aggressive or a gentler approach is appropriate. We also highlight the growing role of newer targeted therapies, including antibody-drug conjugates and bispecific antibodies. These treatments attack lymphoma cells more precisely while sparing healthy tissues. Challenges remain, such as managing treatment side effects, supporting caregivers, and addressing the high cost of new drugs. Nevertheless, by carefully assessing each patient&#x2019;s health and matching them with the right treatment, clinicians aim to achieve the best possible lymphoma control while preserving quality of life.

Colorectal cancer (CRC) is the third most common cancer in the world. Bone metastasis, which occurs in advanced cancer, causes severe damage and accelerates patient death. TROP2, encoded by the TACSTD2 gene, is highly expressed in multiple types of cancer and is associated with tumor proliferation, invasion and metastasis. However, the role of TROP2 in CRC is unclear. TROP2 expression was detected in tumor tissues of CRC patients with or without bone metastases, as well as CRC cell lines. The functional role of TROP2 on CRC cells was validated by in vitro cell culture models and in vivo mouse experiments. Comparative proteomics was used to discover the interactome of TROP2, and later confirmed by immunoprecipitation and immunofluorescent studies. The therapeutic role of TROP2-targeted agent in CRC was verified by intratibial injection mouse models. TROP2 was highly expressed in the tumor tissues of CRC patients, with largely negative expression in the normal counterparts. CRC patients with bone metastasis had even higher TROP2 expression in the tumors than those with primary carcinoma only. We demonstrated that TROP2 promoted the proliferation and migration of CRC cells by in vitro and in vivo experiments, and the pro-invasive and pro-adhesive effects of TROP2 in CRC cells could be enhanced by co-culturing with bone marrow mesenchymal stem cells (BMSCs). Mechanistically, we validated that TROP2 was able to interact with fibronectin (FN) expressed by BMSCs, which increased the expressions of &#x3b1;5, &#x3b1;V, and &#x3b2;3 integrin subunits and facilitated the expression of integrin-linked kinase (ILK) on CRC cells. This interaction was required for the downstream activation of PI3K-Akt signaling and the CRC cell adhesion to BMSCs. Furthermore, intratibial injection mouse experiments verified that TROP2 promoted the colonization of CRC cells in bone marrow, and the combination of the TROP2-targeted antibody-drug conjugate, Sacituzumab Govitecan, and anti-integrin &#x3b1;5&#x3b2;1 monoclonal antibody, Volociximab, was effective in inhibiting bone colonization of CRC cells. TROP2 promotes CRC bone metastasis by interacting with bone marrow-derived FN-integrin axis. Through its adhesive function, TROP2 may coordinate with the specialized bone niche to facilitate metastatic colonization and establish a permissive environment for stromal-tumor interactions. Targeting this axis offers a promising therapeutic strategy for managing bone metastasis in CRC and potentially other TROP2-overexpressing malignancies.

The detection and characterization of hypoxia through functional imaging represents a critical frontier in oncology, cardiology, and neurology. Despite extensive efforts, the clinical translation of a robust hypoxia imaging biomarker remains hindered by suboptimal signal limiting diagnostic accuracy. Here, we report the development of a 64Cu-based radiotracer (64Cu-CysPhe), which exploits the cellular copper uptake pathway involving the human copper transporter 1 (hCtr1). This targeted mechanism facilitates selective tracer accumulation in hypoxic tissues. In-vivo PET-MRI imaging in a murine breast cancer model demonstrated tumor-to-muscle ratios exceeding 3.0 up to 24&#xa0;h post-injection. Notably, immunohistochemical analyses revealed that 64Cu-CysPhe preferentially localizes to hypoxic tumor regions while excluding necrotic cores, thereby providing information about a tumor's immediate microenvironment. Comparative analysis with established radiotracers, including 64Cu-ATSM and 18F-FDG, confirmed the sensitivity of 64Cu-CysPhe in detecting hypoxic tumor regions. These findings establish 64Cu-CysPhe as a promising candidate for non-invasive imaging of tumors.

Oncogenetics focuses on identifying and managing hereditary cancer predisposition, enabling risk-reducing interventions and targeted therapies. This descriptive study evaluated the landscape of oncogenetics training within Medical Genetics Residency Programs in Brazil. Data were collected through online questionnaires and interviews with program supervisors. We assessed rotation availability, timing and duration, clinical and theoretical workload, multidisciplinary care, and competency assessment. Data were analyzed using descriptive statistics. All twelve accredited programs participated. Eleven (92%) offered oncogenetics training, primarily in the third year of residency. While half of the programs provided internal rotations, all allowed external rotations to compensate for local infrastructure limitations. Residents completed a mean of 250.1 practical hours (SD 126.5; range 40-400) over approximately 6.5 months, seeing about 13 patients per week (SD 9.2; range 5-30). Theoretical training averaged 31.3&#xa0;h (SD 26.8; range 4-70), resulting in a mean total training workload of 258.7&#xa0;h (SD 159.1; range 4-470). Multidisciplinary care and research opportunities were common; however, formal competency assessments specific to oncogenetics were infrequent. Considerable variability in workload and clinical settings was observed across programs. The findings indicate that oncogenetics is well integrated into Brazilian medical genetics training, aligning with the growing importance of genomic medicine in oncology. Nevertheless, the marked heterogeneity underscores the need for standardized training approaches. The study suggests that establishing inter-institutional networks and formalizing external rotations may help reduce geographic and technological disparities and support more consistent oncogenetics training in medical genetics residency programs across Brazil.