👤 Sofia Furqan

The significant progress has been made in targeted therapy for lung adenocarcinoma (LUAD) in the past decade. Only few targeted therapeutics have yet been approved for the treatment of lung squamous cell carcinoma (LUSC). Several higher frequency of gene alterations are identified as potentially actionable in LUSC. Our work aimed to explore the complex interplay of multiple genetic alterations and pathways contributing to the pathogenesis of LUSC, with a very low frequency of a single driver molecular alterations to develop more effective therapeutic strategies in the future. We retrospectively analyzed the targeted next-generation sequencing (NGS) data (approximately 600 genes) of 335 patients initially diagnosed with non-small cell lung cancer (NSCLC) at our institution between January 2019 and March 2023 and explored the somatic genome alteration difference between LUSC and LUAD. We analyzed that the presence of loss-of-function (LoF) mutations (nonsense, frameshift, and splice-site variants) in histone-lysine N-methyltransferase 2D ( Our results prompted that somatic LoF mutations of Show less

Fibroblast growth factor receptor (FGFR) alterations drive oncogenesis in multiple tumor types. Here we studied pemigatinib, a selective, potent, oral FGFR1-FGFR3 inhibitor, in the phase 2 FIGHT-207 basket study of FGFR-altered advanced solid tumors. Primary end points were objective response rate (ORR) in cohorts A (fusions/rearrangements, n = 49) and B (activating non-kinase domain mutations, n = 32). Secondary end points were progression-free survival, duration of response and overall survival in cohorts A and B, and safety. Exploratory end points included ORR of cohort C (kinase domain mutations, potentially pathogenic variants of unknown significance, n = 26) and analysis of co-alterations associated with resistance and response. ORRs for cohorts A, B and C were 26.5% (13/49), 9.4% (3/32) and 3.8% (1/26), respectively. Tumors with no approved FGFR inhibitors or those with alterations not previously confirmed to be sensitive to FGFR inhibition had objective responses. In cohorts A and B, the median progression-free survival was 4.5 and 3.7 months, median duration of response was 7.8 and 6.9 months and median overall survival was 17.5 and 11.4 months, respectively. Safety was consistent with previous reports. The most common any-grade treatment-emergent adverse events were hyperphosphatemia (84%) and stomatitis (53%). TP53 co-mutations were associated with lack of response and BAP1 alterations with higher response rates. FGFR1-FGFR3 gatekeeper and molecular brake mutations led to acquired resistance. New therapeutic areas for FGFR inhibition and drug failure mechanisms were identified across tumor types. ClinicalTrials.gov identifier: NCT03822117 . Show less

Concerns remain regarding the heterogeneity in overlapping human immunodeficiency virus (HIV) risk behaviors among sex workers (SWs) in Pakistan; specifically, the degree to which SWs interact with people who inject drugs (PWID) through sex and/or needle sharing.Following an in-depth mapping performed in 2011 to determine the size and distribution of key populations at highest risk of HIV acquisition in Pakistan, a cross-sectional biological and behavioral survey was conducted among PWID, female (FSWs), male (MSWs), and hijra/transgender (HSWs) sex workers, and data from 8 major cities were used for analyses. Logistic regression was used to identify factors, including city of residence and mode of SW-client solicitation, contributing to the overlapping risks of drug injection and sexual interaction with PWID.The study comprised 8483 SWs (34.5% FSWs, 32.4% HSWs, and 33.1% MSWs). Among SWs who had sex with PWID, HSWs were 2.61 (95% confidence interval [CI], 1.19-5.74) and 1.99 (95% CI, 0.94-4.22) times more likely to inject drugs than MSWs and FSWs, respectively. There was up to a 3-fold difference in drug injecting probability, dependent on where and/or how the SW solicited clients. Compared with SWs in Larkana, the highest likelihood of drug injection use was among SWs in Multan (OR = 4.52; 95% CI: 3.27-6.26), followed by those in Lahore, Quetta, and Faisalabad.Heterogeneity exists in the overlapping patterns of HIV risk behaviors of SWs. The risk of drug injection among SWs also varies by city. Some means of sexual client solicitation may be along the pathway to overlapping HIV risk vulnerability due to increased likelihood of drug injection among SWs. There is a need to closely to monitor the mixing patterns between SWs and PWID and underlying structural factors, such as means of sexual client solicitation, that mediate HIV risk, and implement prevention programs customized to local subepidemics. Show less