{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:16:43Z","timestamp":1786637803295,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH Cancer Center Support Grant","award":["3P30CA022453-41S1"],"award-info":[{"award-number":["3P30CA022453-41S1"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>Myelodysplastic neoplasms (MDS) are characterized by remarkable heterogeneity in clinical manifestations, posing significant management challenges arising due to genetic plasticity. While the Revised International Prognostic Scoring System (IPSS-R) has traditionally stratified MDS into higher-risk (HR) and lower-risk (LR) categories, the recently developed Molecular International Prognostic Scoring System (IPSS-M) integrates molecular signatures and has further enhanced prognostic stratification. In LR-MDS, current therapeutic interventions remain non-curative and the goal of treatment is centered along three critical axes: reducing transfusion dependence, improving quality of life, and reducing the risk of progression to acute myeloid leukemia (AML). This review examines recent progress made in the therapeutic landscape of LR-MDS, with particular emphasis on the molecular basis of these novel agents that may have disease-modifying potential. We evaluate the clinical trials and targeted agents in the pipeline for treating LR-MDS, providing a comprehensive perspective where these treatment modalities are placed in the current standard of care and how these novel targets can shape future therapeutic innovations.<\/jats:p>","DOI":"10.3390\/cancers17223610","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T11:47:27Z","timestamp":1762775247000},"page":"3610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Molecular Insights and Therapeutic Advances in Low-Risk Myelodysplastic Neoplasms: A Clinical Review"],"prefix":"10.3390","volume":"17","author":[{"given":"Vikram","family":"Dhillon","sequence":"first","affiliation":[{"name":"Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw","family":"Maciejewski","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9044-1309","authenticated-orcid":false,"given":"Suresh Kumar","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/jha2.523","article-title":"Lower-risk myelodysplastic syndromes: Current treatment options for anemia","volume":"3","author":"Meunier","year":"2022","journal-title":"eJHaem"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.1182\/blood.V126.23.5224.5224","article-title":"GDF11 Increased in Patients with Myelodysplastic Syndrome","volume":"126","author":"Han","year":"2015","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nm.3512","article-title":"Transforming growth factor-\u03b2 superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis","volume":"20","author":"Suragani","year":"2014","journal-title":"Nat. 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