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This study evaluates guadecitabine, a hypomethylating agent, combined with carboplatin as a second-line treatment for extensive-stage SCLC using peripheral blood mononuclear cell (PBMC) samples collected at baseline and during treatment. Methylome analyses identify global hypomethylation and pathway shifts linked to tumor progression, immune response, and resistance, including changes in immune-cell 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epigenetic process is the study focused on in SCLC patients?","Question",{"text":63,"@type":64},"The study focuses on DNA methylation changes in peripheral blood mononuclear cells (PBMCs) under hypomethylating therapy.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was PBMC DNA methylation measured?",{"text":68,"@type":64},"PBMC DNA was analyzed using Infinium HumanMethylationEPIC v1.0 bead chips, followed by identification of differentially methylated positions.",{"name":70,"@type":61,"acceptedAnswer":71},"What immune-related finding is reported from deconvolution analysis?",{"text":72,"@type":64},"Deconvolution analysis indicates a higher proportion of monocytes in cycle 1 day 1 (pre-treatment) versus normal PBMCs, with immune-cell composition changing after hypomethylating 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[https://doi.org/10.64898/2026.02.18.706553](https://doi.org/10.64898/2026.02.18.706553); this version posted February 19, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \nEffects of the Hypomethylating Agent Guadecitabine on Peripheral Blood Mononuclear Cell Methylomes and Immune Cell Populations in Small-Cell Lung Cancer Patients  \nElnaz Abbasi Farid1* ,Shu Zhang 1* , Zhen Fu2 , Collin M. Coon 1 , Daniela Matei3 , Shadia I. Jalal5,6*\\# Kenneth P. Nephew1,4,5\\#  \n1 Medical Sciences Program, Indiana University School of Medicine-Bloomington, Bloomington, IN 47405, USA  \n2 Bioinformatics and Biostatistics Core, Van Andel Institute, Grand Rapids, MI 49505, USA 3 Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University Chicago, IL, USA  \n4 Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA  \n5 Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA  \n6 Department of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN4 6202, USA  \n* Equal contribution  \n\\#Corresponding authors Kenneth P. Nephew, PhD  \n302 Biology Building; 1001 E. 3rd St  \nIndiana University School of Medicine-Bloomington  \nBloomington, IN 47405  \n[knephew@iu.edu](knephew@iu.edu)  \n[Shadia I. Jalal](Shadia I. Jalal) , MD  \nIndiana University Melvin and Bren and Simon Comprehensive Cancer Center  \n535 Barnhill Drive; RT473  \nIndianapolis, IN 46202  \n[sjalal@iu.edu](sjalal@iu.edu)  \nRunning title: PBMC methylomes in SCLC patients  \nKey words: Small cell lung cancer, peripheral blood mononuclear cells (PBMCs), DNA  \nmethylation, epigenetics, platinum resistance  \nbioRxiv preprint doi: [https://doi.org/10.64898/2026.02.18.706553](https://doi.org/10.64898/2026.02.18.706553); this version posted February 19, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \nSummary  \nMethylome changes in peripheral blood mononuclear cell (PBMCs) from small cell lung cancer  \n(SCLC) patients treated with an epigenetic therapy revealed global hypomethylation and altered cancer signaling processes associated with tumor progression, immune response, therapy resistance and significant change in the proportion of immune cells. Integrating blood-based methylation biomarkers into clinical trials of epigenetic therapy and methylomic analysis of PBMCs provides direct monitoring of treatment effects in cancer patients, which may improve patient selection and enable real-time response assessment in patients receiving hypomethylating agents.  \nbioRxiv preprint doi: [https://doi.org/10.64898/2026.02.18.706553](https://doi.org/10.64898/2026.02.18.706553); this version posted February 19, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \nAbstract  \nBackground  \nSmall-cell lung cancer (SCLC) represents 15% of lung cancers and with a 5-year survival rate under 7% remains one of the deadliest malignancies. Although initially responsive to  \nchemotherapy, rapid recurrence and resistance are common. Epigenetic modifications,  \nparticularly DNA methylation, contribute to tumor progression and therapy resistance.  \nGuadecitabine, a hypomethylating agent (HMA), has shown promising clinical activity when combined with carboplatin in preclinical models. We evaluated the combination of guadecitabine with carboplatin as a se","cbCaibdsph259REr","https://ap.wps.com/l/cbCaibdsph259REr","pdf",1430759,28,"English","# Summary\n# Abstract\n## Background\n## Results","[{\"question\":\"What epigenetic process is the study focused on in SCLC patients?\",\"answer\":\"The study focuses on DNA methylation changes in peripheral blood mononuclear cells (PBMCs) under hypomethylating therapy.\"},{\"question\":\"How was PBMC DNA methylation measured?\",\"answer\":\"PBMC DNA was analyzed using Infinium HumanMethylationEPIC v1.0 bead chips, followed by identification of differentially methylated positions.\"},{\"question\":\"What immune-related finding is reported from deconvolution analysis?\",\"answer\":\"Deconvolution analysis indicates a higher proportion of monocytes in cycle 1 day 1 (pre-treatment) versus normal PBMCs, with immune-cell composition changing after hypomethylating treatment.\"}]","Effects of the Hypomethylating Agent Guadecitabine on Peripheral Blood Mononuclear Cell Methylomes and Immune Cell Populations in Small-Cell Lung Cancer Patients | PDF",1790099802,71]