Department of Biochemistry

Background/Objectives: Time to treatment initiation (TTI) has been identified as a predictor of survival in many cancers, but its impact on malignant pleural mesothelioma (MPM) is unknown. This study investigates factors influencing TTI in MPM and its association with overall survival. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to obtain data for MPM patients in the United States. TTI was defined as the number of days from diagnosis to initiation of first treatment, and delayed TTI was defined as exceeding the median TTI. Χ2 tests and t-tests compared sociodemographic and clinical differences between early and delayed TTI groups, while Kaplan–Meier and Cox proportional hazards models evaluated relationships between prognostic factors, TTI, and survival. Results: Among 4879 MPM patients, the median TTI was 39 days. Median survival was 10 months among early TTI patients and 13 months among delayed TTI patients. Patients with epithelioid histology were more likely to have delayed TTI, as were patients who received combination therapy or were diagnosed more recently (p < 0.0001). Adjusting for covariates, delayed TTI status remained associated with better survival (HR 0.79, 95% CI: 0.74–0.84). Conclusions: This study presents an important insight into the management of MPM, demonstrating that delayed time to treatment initiation is positively associated with improved overall survival, contrary to findings in most cancers. This finding underscores the importance of comprehensive, multidisciplinary care, as delays due to robust staging evaluations and patient travel to high-volume centers of excellence likely contribute to delays in treatment. Taken together, these results suggest that clinicians should prioritize personalized treatment planning and collaborative care over a push to rapidly initiate treatment to optimize patient outcomes in MPM.

Background/Objectives: Pentraxin 3 (PTX3), a member of the pentraxin superfamily, plays diverse roles in immunity and inflammation. Its dual role in tumorigenesis, exhibiting both protumoral and antitumoral effects, has been the subject of conflicting reports. High PTX3 expression levels in serum and tumor tissues have been associated with poor prognosis in various malignancies, suggesting its potential as a prognostic biomarker. Through this meta-analysis, we aim to comprehensively assess the prognostic significance of PTX3 protein expression in human malignancies and evaluate its potential as a pan-cancer prognostic marker. Methods: A systematic literature search was conducted across the PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library databases. Studies were included if they assessed the association between PTX3 protein expression and overall survival (OS) in cancer patients. Hazard ratios (HRs) were pooled using a random-effects model. Subgroup analyses were performed based on the method of PTX3 assessment, and publication bias was evaluated using Egger’s and Begg’s tests. Results: Nine studies encompassing 1215 patients were included in the analysis. High PTX3 expression was significantly associated with poorer OS (HR = 1.89, 95% CI = 1.55–2.32, p < 0.01) with no significant heterogeneity (I2 = 0%). Subgroup analysis revealed consistent results across different assessment methods (immunohistochemistry: HR = 1.93, p < 0.01; immunoassay: HR = 1.86, p < 0.01). However, publication bias was detected (Egger’s test, p = 0.03). Conclusions: High PTX3 protein expression is associated with a poor prognosis in various malignancies, supporting its potential as a prognostic biomarker.

Introduction: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, despite advances in immune checkpoint inhibitors and targeted therapies. Antibody–drug conjugates (ADCs) represent a promising therapeutic approach by delivering cytotoxic agents specifically to cancer cells, potentially reducing harm to healthy tissues. This study aims to explore the effectiveness and challenges associated with ADCs in NSCLC, with a focus on drug-induced interstitial lung disease (D-ILD). Methods: A comprehensive literature review was conducted across MEDLINE (Ovid), Embase (Elsevier), CENTRAL (Cochrane Library), and other sources up to March 2023, to identify ADCs used in NSCLC treatment and their associated risk of D-ILD. The incidence of ILD was analyzed from clinical trial data, while ADC target expression was examined through RNA and protein levels in normal and tumor lung tissues. Discussion: Our findings highlight the therapeutic potential of ADCs in NSCLC, as evidenced by significant clinical outcomes. However, the occurrence of D-ILD presents a notable challenge, as its incidence was not directly correlated with the expression levels of the target antigens. This suggests that D-ILD may result from factors beyond antigen expression, including the cytotoxic payload and linker characteristics of ADCs. Conclusion: ADCs offer a promising avenue for NSCLC treatment. Nonetheless, the risk of D-ILD necessitates a balanced approach in ADC development, focusing on optimizing linker and payload properties to mitigate this adverse effect. Further research is essential to better understand and manage D-ILD, ensuring the safe and effective use of ADCs in clinical practice.