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Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential. Molecules 2024, 29, 4280 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules29174280  \nReceived: 1 August 2024  \nRevised: 4 September 2024  \nAccepted: 6 September 2024  \nPublished: 9 September 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Faculty of Health Science, Powi´sle University, 80-214 Gda ´nsk, Poland  \n2 Department of Biochemistry, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland; [bhaskar.pradhan@wum.edu.pl](bhaskar.pradhan@wum.edu.pl)  \n3 Department of Biochemistry and Clinical Chemistry, Faculty of Biology, Medical University of Warsaw, 02-097 Warsaw, Poland  \n4 Department Medical Biology and Genetics, Faculty of Biology, University of Gda ´nsk, 80-308 Gda ´nsk, Poland  \n5 Department of Hematology and Transplantology, Faculty of Medicine, Medical University of Gda ´nsk, 80-214 Gda ´nsk, Poland; [andrzej.hellmann@gumed.edu.pl](andrzej.hellmann@gumed.edu.pl)  \n* Correspondence: [24556@gumed.edu.pl](24556@gumed.edu.pl) (J.J.L.); [joanna.jakobkiewicz-banecka@biol.ug.edu.pl](joanna.jakobkiewicz-banecka@biol.ug.edu.pl) (J.J.-B.)† These authors contributed equally to this work and share first authorship.  \nAbstract: In this review we explore innovative approaches in the treatment of hematologic cancers by combining various therapeutic modalities. We discuss the synergistic potential of combining inhibitors targeting different cellular pathways with immunotherapies, molecular therapies, and hormonal therapies. Examples include combining PI3K inhibitors with proteasome inhibitors, NF-κB inhibitors with immunotherapy checkpoint inhibitors, and neddylation inhibitors with therapies targeting the tumor microenvironment. Additionally, we discuss the potential use of small molecules and peptide inhibitors in hematologic cancer treatment. These multidimensional therapeutic combinations present promising strategies for enhancing treatment efficacy and overcoming resistance mechanisms. However, further clinical research is required to validate their effectiveness and safety profiles in hematologic cancer patients.  \nKeywords: hematologic cancers; innovative approaches; therapeutic modalities; synergistic potential; PI3K inhibitors; proteasome inhibitors; NF-κB inhibitors; immunotherapy checkpoint inhibitors; neddylation inhibitors; small molecules  \n1. Introduction  \nHematologic malignancies (HMs), encompassing a diverse array of cancers affecting blood, bone marrow, and lymph nodes, present a significant clinical challenge due to their heterogeneity and propensity for treatment resistance [1,2] . In 2020, the global incidence of leukemia was approximately 474,519 new cases, according to GLOBOCAN data from the International Agency for Research on Cancer (IARC) . This represents about 2.6% of all new cancer cases worldwide [3] . NHL had an estimated 544,352 new cases in 2020, while HL accounted for about 83,087 new cases [4] . Despite advances in therapy, achieving durable remissions remains elusive in many cases. Traditional treatments for hematologic malignancies include chemotherapy, radiotherapy, stem cell transplantation (SCT), and therapeutic antibodies [5,6] . However, these approaches often lead to adverse effects such as organ damage, fatigue, na","cbCairob3j5k9C08","https://ap.wps.com/l/cbCairob3j5k9C08","pdf",1870056,"English","# Introduction\n## Therapeutic challenges in hematologic malignancies\n## Traditional treatments and limitations\n## Emerging multimodal strategies","[{\"question\":\"What therapeutic combinations does the review emphasize for hematologic malignancies?\",\"answer\":\"The review emphasizes combining pathway-targeted inhibitors with immunotherapies, molecular therapies, and hormonal therapies. It highlights specific synergy examples such as PI3K inhibitors with proteasome inhibitors and NF-κB inhibitors with checkpoint inhibitors.\"},{\"question\":\"Why are multimodal strategies considered promising in this field?\",\"answer\":\"Multimodal strategies aim to enhance treatment efficacy and overcome resistance mechanisms. By leveraging synergistic effects across different therapeutic pathways, they seek to improve durability of responses.\"},{\"question\":\"Are the proposed strategies already fully proven in patients?\",\"answer\":\"Further clinical research is required to validate the effectiveness and safety profiles. The review notes that additional evidence is needed for hematologic cancer patients.\"}]","Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential | PDF",1790004008,101]