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.

Liver transplantation is a critical and evolving field in modern medicine, offering life-saving treatment for patients with end-stage liver disease and other hepatic conditions. Despite its transformative potential, transplantation faces persistent challenges, including a global organ shortage, increasing liver disease prevalence, and significant waitlist mortality rates. Current donor evaluation practices often discard potentially viable livers, underscoring the need for refined graft assessment tools. This review explores advancements in graft evaluation and utilization aimed at expanding the donor pool and optimizing outcomes. Emerging technologies, such as imaging techniques, dynamic functional tests, and biomarkers, are increasingly critical for donor assessment, especially for marginal grafts. Machine learning and artificial intelligence, exemplified by tools like LiverColor, promise to revolutionize donor-recipient matching and liver viability predictions, while bioengineered liver grafts offer a future solution to the organ shortage. Advances in perfusion techniques are improving graft preservation and function, particularly for donation after circulatory death (DCD) grafts. While challenges remain—such as graft rejection, ischemia-reperfusion injury, and recurrence of liver disease—technological and procedural advancements are driving significant improvements in graft allocation, preservation, and post-transplant outcomes. This review highlights the transformative potential of integrating modern technologies and multidisciplinary approaches to expand the donor pool and improve equity and survival rates in liver transplantation.

The fusion of penetrating peptides (PPs), e.g., cell penetration peptides (CPPs) or antimicrobial peptides (AMPs), together with antimicrobial agents is an expanding research field. Specific AMPs, such as lactoferricin B (LfcinB), have demonstrated strong antibacterial, antifungal, and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and an antimicrobial agent. This is especially necessary in cancer treatment, where microbial infections pose a critical risk. Leukemic cells frequently exhibit altered outer lipid membranes compared to healthy cells, making them more sensitive to compounds that interfere with their membrane. In this study, we revisited and reanalyzed our earlier research on LfcinB and its conjugates. Furthermore, we carried out new experiments with a specific focus on cell proliferation, changes in membrane asymmetric phosphatidylserine location, intracellular reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition.

Very Small Embryonic-like Stem Cells (VSELSCs) and Very Small Cancer Stem Cells (VSCSCs) are fields of intensive research. Although the presence in vitro of VSELSC and VSCSC cellular stage analogs appear probable, it has yet to be published. Utilizing established human cell cultures with varying populations of primitive cells, stained with CD markers specific to primitive stages, in addition to a fluorescent DNA dye, and following histochemical processing, we have developed a cytological method for detecting Very Small Leukemic Stem-like Cells (VSLSLCs), Very Small Cancer Stem-like Cells (VSCSLCs), and VSELSCs. This detection provides an opportunity to advance research in these areas.

The fusion of penetrating peptides (PPs), e.g., cell penetration peptides (CPPs), or antimicrobial peptides (AMPs) together with antimicrobial agents is an expanding research field. Specific AMPs, such as lactoferricin B (LfcinB), have demonstrated strong antibacterial, antifungal, and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and an antimicrobial agent. This is especially necessary in cancer treatment where microbial infections pose a critical risk. Leukemic cells frequently exhibit altered outer lipid membranes compared to healthy cells, making them more sensitive to compounds that interfere with their membrane. In this communication, we revisited and reanalyzed our earlier research on LfcinB and its conjugates. Furthermore, we carried out new experiments with a specific focus on cell proliferation, changes in membrane asymmetric phosphatidylserine location, intracellular reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition.

Ferroptosis is an iron-dependent form of regulated cell death driven by phospholipid peroxidation and the failure of cellular antioxidant defenses. Its close integration with iron metabolism, lipid remodeling, and redox homeostasis has identified ferroptosis as a potentially exploitable vulnerability in cancer. This review critically examines the molecular and pharmacological determinants of ferroptotic sensitivity, including iron handling, acyl-CoA synthetase long-chain family member 4 (ACSL4)/lysophosphatidylcholine acyltransferase 3 (LPCAT3)-dependent lipid remodeling, and the glutathione peroxidase 4 (GPX4)–glutathione, ferroptosis suppressor protein 1 (FSP1)–coenzyme Q10, mitochondrial dihydroorotate dehydrogenase (DHODH), and GTP cyclohydrolase 1 (GCH1)–tetrahydrobiopterin defense systems. We discuss experimental ferroptosis inducers and clinically used drugs with reported ferroptosis-modulating activity, emphasizing differences in their mechanisms, strength of evidence, and translational relevance. Particular attention is given to the bidirectional interactions between ferroptosis and the tumor immune microenvironment. Although cytotoxic lymphocytes and interferon-gamma (IFN-γ) signaling may sensitize malignant cells to ferroptosis, excessive lipid peroxidation in cluster of differentiation 8-positive (CD8⁺) T cells, natural killer cells, dendritic cells, and other immune populations may impair antitumor immunity. These context- and cell-type-dependent effects support combination strategies involving immunotherapy, radiotherapy, and conventional or targeted anticancer treatments, but also define potential toxicities. We further discuss candidate biomarkers related to iron metabolism, lipid composition, antioxidant capacity, and immune context, as well as the need for patient stratification and targeted drug delivery. Successful clinical implementation will require selective induction of ferroptosis in malignant cells while preserving normal tissues and antitumor immune function. Ferroptosis should therefore be regarded as a conditional therapeutic vulnerability rather than a universally beneficial anticancer mechanism.