Search Results (287)

Cellular responses depend on the coordinated regulation of receptor activation, trafficking, and signaling across distinct membrane and intracellular compartments. Proteoglycans (PGs), traditionally regarded as structural components of the extracellular matrix and co-receptors, are now emerging as active organizers of receptor dynamics. This review examines the mechanisms through which PGs regulate receptor trafficking and spatial signaling in cancer. Recent studies addressing the roles of proteoglycans in receptor clustering, endocytic pathway selection, intracellular trafficking, recycling, lysosomal degradation, endosomal signaling, exosome biogenesis, and nuclear receptor transport were evaluated, with particular attention to the strength of direct evidence for trafficking. Particular attention was given to the complementary functions of proteoglycan core proteins, glycosaminoglycan chains, and extracellular matrix remodeling in shaping receptor behavior. Current evidence demonstrates that proteoglycans govern multiple stages of receptor biology by controlling ligand presentation, receptor accessibility, membrane organization, intracellular trafficking, and signaling persistence. Individual proteoglycans exert distinct effects on receptor fate, ranging from receptor downregulation and degradation to sustained endosomal signaling and nuclear receptor translocation. Cancer-associated alterations in proteoglycan expression, glycosaminoglycan sulfation, heparanase activity, ectodomain shedding, and glycocalyx organization remodel signaling networks, strengthen communication between tumor and stromal cells, and promote tumor progression, immune modulation, metastasis, and therapeutic resistance. Proteoglycans have emerged as fundamental regulators of receptor trafficking and signaling architecture. Through the integration of extracellular matrix organization with receptor dynamics, they shape the spatial and temporal properties of oncogenic signaling. This conceptual framework broadens our understanding of tumor biology and identifies proteoglycan-dependent regulation of receptor trafficking as a promising avenue for future therapeutic intervention. Full article

Copper is essential for mitochondrial respiration, antioxidant defense, extracellular matrix maturation, and cellular signaling, yet disturbances in its abundance or intracellular distribution can damage the kidney through mechanistically distinct pathways. Cuproptosis is a specific copper-dependent form of regulated cell death in which copper binds lipoylated mitochondrial proteins, promotes aggregation of tricarboxylic acid cycle components, destabilizes iron–sulfur cluster proteins, and elicits FDX1- and protein lipoylation-dependent proteotoxic stress. This mechanism should be distinguished from broader copper-associated injury, including redox imbalance, glutathione depletion, respiratory-chain inhibition, senescence, apoptosis, and lysyl oxidase-mediated matrix remodeling. This narrative review examines how renal copper uptake, trafficking, and compartmentalization interact with cell-specific metabolism to shape copper-related cell fates across acute kidney injury, nephrotoxicity, renal ischemia–reperfusion injury, crystal- and lipid-related tubular injury, diabetic kidney disease, podocyte injury, chronic kidney disease and renal fibrosis, end-stage renal disease, renal cell carcinoma, and hereditary copper disorders. Mechanistic evidence is strongest in selected acute tubular, crystal-injury, and renal cancer models, in which transporter manipulation, DLAT oligomerization, iron–sulfur perturbation, or functional rescue has been demonstrated. In chronic kidney disease and fibrosis, copper-DLAT interactions, complex IV inhibition, COMMD1-SOD1 dysfunction, and ATP7A-FBLN4-LOX signaling establish pathogenic copper dependence but do not yet demonstrate a complete canonical cuproptosis pathway. By integrating disease-specific evidence with the molecular determinants of copper handling and protein lipoylation, this review identifies current therapeutic opportunities, candidate biomarkers, and key research priorities while preserving the distinction between cuproptosis and other forms of copper-associated kidney injury. Full article

Collagen, long regarded as the inert structural scaffold of the extracellular matrix, is now recognised as a source of bioactive signaling molecules: enzymatic hydrolysis releases low-molecular-weight bioactive collagen peptides that act systemically. This narrative review synthesises in vitro, animal-model, and veterinary clinical evidence with explicit differentiation of evidence levels; literature was identified through structured searches of PubMed, Web of Science, and Google Scholar, covering peer-reviewed, English-language reports published between 2000 and January 2026, without a formal systematic protocol. Across rodent, porcine, and human pharmacokinetic studies, orally administered collagen hydrolysate is efficiently absorbed, with a fraction reaching the circulation as intact prolyl-hydroxyproline and hydroxyprolyl-glycine through the conserved PEPT1/PEPT2 transporters; reported bioavailability varies with source, dose, and method, so no single value generalises across species. Native collagen and larger collagen fragments engage structure-dependent receptors in vitro (α2β1 integrins, DDR1/DDR2, GPVI, LAIR-1/2) that require triple-helical or Gly-Pro-Hyp presentation, whereas it is not established that the di- and tripeptides that reach the circulation after oral dosing engage them; their systemic actions are partly attributable to intracellular routes, including the Keap1–Nrf2 axis, HDAC/HAT modulation, and glycine-dependent glutathione synthesis. The gut–collagen peptide axis, a model derived from rodent and cell-culture data, links microbial bile acid remodeling and FXR/TGR5 signaling to systemic effects. Current evidence supports validated use in canine and equine osteoarthritis; species-specific bioavailability studies in dogs and cats remain the priority. Full article

Conventional antibiotics exhibit limited ability to penetrate host cell membranes, making intracellular bacterial infections difficult to eradicate completely. As naturally derived nanoscale membrane structures, bacterial extracellular vesicles (EVs) possess excellent biocompatibility and intrinsic transmembrane transport capability, thereby demonstrating unique advantages for in vivo drug delivery. The present study investigated the feasibility of using EVs derived from the avirulent Streptococcus suis T15 as novel carriers for ciprofloxacin delivery. We also comprehensively evaluated the biosafety and anti-infective efficacy of this nanodrug delivery system in vitro and in vivo. Cytotoxicity assays, live/dead cell staining, and hemolysis analyses demonstrated that T15-derived EVs at concentrations below 50 μg/mL did not cause significant cellular damage or hemolysis. Serum biochemical analyses in mice further confirmed the absence of obvious organ toxicity, indicating favorable biosafety within the tested concentration range. Ciprofloxacin was successfully loaded into EVs using a combination of ultrasonication and electroporation, achieving a drug concentration of 438.6 μg/mL and a loading efficiency of 10.96%. The ciprofloxacin-loaded EVs (EV-CIP) exhibited significantly greater antibacterial activity than free ciprofloxacin against both intracellular bacteria and fluoroquinolone-resistant strains exhibiting efflux pump activity. Evaluation in animal infection models showed that EV-CIP markedly reduced mortality in infected Galleria mellonella larvae. It also decreased bacterial burdens in multiple mouse organs and significantly alleviated histopathological damage. These results collectively suggest that EVs derived from the avirulent S. suis T15 were safe and effective within the tested concentration range and experimental conditions. The EV-based ciprofloxacin delivery system substantially enhanced the clearance of intracellular pathogens and fluoroquinolone efflux pump-positive bacteria, suggesting its potential application in the treatment of difficult-to-treat bacterial infections. This study provides a theoretical and experimental basis for the further development of novel EV-based anti-infective drug delivery strategies for livestock and poultry. Full article

Mitochondrial dysfunction and impairment of high-energy phosphate transfer are increasingly recognised as shared pathogenic features across neurological disorders. Because neurons require large amounts of ATP to sustain synaptic transmission, ion gradients, axonal transport, and intracellular signalling, they are especially vulnerable to disturbances in energy metabolism. Neurological dysfunction, therefore, cannot be explained solely by reduced mitochondrial ATP production. It also involves failure of the creatine kinase/phosphocreatine (CK/PCr) and adenylate kinase/AMP-activated protein kinase (AK–AMPK) systems, which normally support local ATP buffering, high-energy phosphate transfer, and intracellular energy homeostasis. In parallel, extracellular ATP-dependent purinergic dysregulation contributes to glia-mediated inflammation, synaptic dysfunction, and cell death, linking intracellular energy failure to abnormal intercellular signalling. In this review, we integrate these mechanisms into a shared pathological continuum of disrupted energy homeostasis. We then compare Alzheimer’s disease, Parkinson’s disease, and epilepsy as representative disorders with shared and disease-specific manifestations of this continuum, characterised respectively by chronic cerebral energy crisis, selective metabolic fragility, and acute energy overload with purinergic dysregulation. Finally, we discuss how this comparative perspective may help identify shared therapeutic opportunities while preserving disorder-specific interpretation. Full article

Gemcitabine-based chemotherapy has long served as a standard treatment for urothelial carcinoma (UC), particularly in perioperative and metastatic settings. However, therapeutic efficacy is frequently limited by intrinsic or acquired resistance. Gemcitabine functions as a prodrug whose activity depends on coordinated processes involving cellular uptake, intracellular activation, metabolic inactivation, and nucleotide metabolism. Increasing evidence suggests that resistance in UC is mediated by multiple interconnected mechanisms beyond alterations in gemcitabine transport, activation, and inactivation alone. Key molecular determinants include human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), cytidine deaminase (CDA), and ribonucleotide reductase regulatory subunit M1 (RRM1), which is involved in nucleotide pool maintenance and DNA synthesis. In addition, replication stress responses, apoptosis evasion pathways, and tumor microenvironment-associated factors also contribute to gemcitabine resistance. Stress-adaptive pathways involving Y-box binding protein 1 (YB-1), hypoxia-inducible factor-1 alpha (HIF-1α), and autophagy-related mechanisms may further promote survival under chemotherapy-induced stress conditions. In addition, extracellular mucin-associated mechanisms may alter intratumoral drug accessibility and contribute to resistance. In this review, we summarize UC-specific evidence regarding gemcitabine resistance and discuss how these pathways collectively shape an integrated resistant phenotype. Full article

Magnetic targeting of drug carriers is commonly studied at macroscopic scales, while its impact on drug transport across individual cell membranes remains poorly quantified. Here, we present a theoretical and numerical model of magnetically assisted drug transport across the membrane of a single tumor cell exposed to magnetic field gradients. Extracellular transport is described by an advection–diffusion equation that couples passive diffusion with magnetophoretic drift, whereas intracellular transport is governed by diffusion and first-order uptake kinetics. The cell membrane is modeled as a semi-permeable interface with finite permeability, providing explicit coupling between extracellular and intracellular domains. Assuming spherical symmetry, the coupled transport equations are solved using finite-difference schemes, with magnetic forcing represented through an effective drift velocity $v_{\mathrm{m}\mathrm{a}\mathrm{g}}$ and interpreted using the magnetic Peclet number. To enable a controlled comparison between healthy and tumor cells, identical geometric, diffusive, and magnetic parameters are used, while biological differences are introduced solely through membrane permeability and intracellular uptake rates. By separating cumulative membrane delivery from cumulative intracellular uptake, the model resolves ambiguities arising from heterogeneous uptake kinetics. The results show that magnetophoretic drift enhances near-membrane drug accumulation and effective transmembrane flux without modifying intrinsic membrane properties. Magnetic targeting therefore acts as a transport amplifier, magnifying pre-existing biological differences and producing a larger model-predicted delivery advantage in tumor cells. Overall, the framework identifies the magnetic Peclet number as the key parameter governing the transition from diffusion-dominated to drift-enhanced cellular drug transport. Full article

This study aimed to investigate the regulatory effect and cryoprotective mechanism of melatonin (MT) on the physiological functions of Lactobacillus plantarum FQR during freezing and freeze-drying. Results indicated that the addition of 5 mg/mL MT as a cryoprotectant maximized the freeze-drying survival rate to 32.04 ± 2.14%. MT effectively alleviated low-temperature and freeze-drying stress by reducing extracellular alkaline phosphatase activity, enhancing intracellular lactate dehydrogenase activity, and decreasing extracellular β-galactosidase activity without significant differences. Higher survival rates in defining medium further suggested that MT reduced damage to cell wall and membrane structures during lyophilisation, decreased membrane permeability, and preserved cellular physiological functions. In addition, MT supported cellular energy metabolism and protein synthesis, enhanced transmembrane potential to facilitate ATP transport, and helped maintain intracellular and extracellular pH balance. The prepared freeze-drying protectant containing 69.80 mg/mL exopolysaccharides (EPS) and 4.25 mg/mL MT showed better protective effects than the control group. MT also increased bound water content, lowered the freezing point of the solution, and inhibited ice crystal formation. Transcriptomic analysis revealed that amino acid biosynthesis, amino acid metabolism, and ABC transport systems were the primary pathways affected by MT treatment. These findings demonstrate that MT improves freeze-drying tolerance by maintaining membrane integrity, regulating cellular metabolism, and enhancing oxidative stress resistance. Given its natural biosynthetic origin, generally recognized as safe (GRAS) status, and absence of residual solvents or allergenic proteins, MT can be safely considered for incorporation into food and nutraceutical products. This study underscores the practical relevance of MT as a functional component in compound cryoprotectants, providing a feasible strategy to enhance the viability, stability, and industrial applicability of Lactobacillus plantarum during freeze-drying and storage. Full article

Intraoperative fluorescence-guided surgery is an important adjunct to brain tumor resection. However, fluorescent probe performance varies across molecularly and histopathologically distinct entities, including IDH-wildtype glioblastoma, metastatic brain tumors (MBTs), and primary central nervous system lymphoma (PCNSL), and the mechanisms underlying this variability remain poorly understood. We propose a mechanistic framework integrating biomechanical constraints, molecular barrier heterogeneity, and probe-specific pharmacokinetics to explain cross-tumor differences in fluorescence signal. Probe performance is conceptualized through three sequential bottlenecks: extravasation (blood–brain barrier/blood–tumor barrier permeability and transcytosis), interstitial penetration (extracellular matrix density and hydraulic resistance), and retention/clearance (efflux transporters and metabolic processing). An overlying optical layer, including tissue absorption, scattering, and autofluorescence, further modulates the detected signal. Tumor-specific molecular heterogeneity critically shapes these processes. In IDH-wildtype glioblastoma and legacy high-grade glioma cohorts, heterogeneous expression of ATP-binding cassette transporters has been associated with reduced intracellular accumulation of protoporphyrin IX after 5-aminolevulinic acid administration and may contribute to false-negative fluorescence in selected tumor regions. In MBTs, stage-dependent blood–tumor barrier integrity and vascular programs influence probe delivery, whereas in PCNSL, corticosteroid-sensitive restoration of endothelial barrier function may compromise the performance of leakage-dependent tracers. Together, this framework highlights how tumor biology, barrier function, and probe pharmacology jointly shape fluorescence contrast. Rational probe selection informed by tumor-specific transport and barrier constraints may improve intraoperative visualization of brain tumors and optimize surgical decision-making. Full article

Advances in mass spectrometry-based metabolomics have enabled the detection of numerous small molecules in biological systems, revealing complex metabolic alterations associated with cancer. Among these, dipeptides are consistently detected in plasma, serum, and tumor tissue metabolomic profiles, yet their biological significance is not fully understood. In most studies, circulating dipeptides are interpreted as nonspecific byproducts of protein degradation generated during increased proteolysis. However, accumulating evidence suggests that at least some endogenous dipeptides may have biological activities, including antioxidant effects, metabolic modulation, and potential signaling functions. In this review, we examine the possible origins, transport mechanisms, and biological implications of circulating dipeptides in cancer metabolomics. We discuss multiple sources of dipeptide generation, including intracellular proteolysis, autophagy, extracellular matrix remodeling, tumor cell death, host tissue catabolism, and microbiome metabolism. We also summarize current knowledge regarding peptide transport systems and intracellular dipeptide metabolism that may regulate the fate of these molecules within mammalian systems. In addition, evidence supporting the biological activities of certain endogenous dipeptides is reviewed to evaluate the possibility that some circulating dipeptides may function as bioactive metabolites. Finally, we propose conceptual frameworks for interpreting circulating dipeptides in cancer, including their potential roles as indicators of protein turnover, intermediates in amino acid recycling, stress-buffering molecules, metabolic signals, or components of tumor–host metabolic communication. A better understanding of circulating dipeptides may provide new insights into cancer metabolism and reveal previously overlooked metabolite classes with potential biomarker or functional significance. Full article

Phosphate (Pi) and calcium (Ca²⁺) are essential mineral ions that play coordinated roles in maintaining normal cellular functions. While various steps of calcium signaling are well characterized, emerging evidence suggests the critical role of both intracellular and extra cellular phosphate in regulating intracellular Ca²⁺. In the cytoplasm, phosphate influences ATP production and organelle calcium buffering and influences the activity of calcium pumps, such as sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA) and the plasma membrane Ca²⁺-ATPase (PMCA). Extracellular phosphate, taken up via sodium-dependent phosphate transporters, triggers signaling cascades that affect the processes of calcium influx, storage, and release. Additionally, high extracellular phosphate levels can disrupt calcium homeostasis through the systemic interactions of hormones such as fibroblast growth factor 23 (FGF23), vitamin D and parathyroid hormone (PTH), especially under pathological conditions such as chronic kidney disease (CKD). This article briefly summarizes the current understanding of the bidirectional influence of intra- and extracellular phosphate on calcium dynamics at the cellular level, with a focus on the underlying mechanisms. Full article

Vasculogenic mimicry (VM) is the ability of cancer stem cells (CSCs) to express an endothelial-like phenotype and participate in tumor neovascularization via the formation of a blood-conducting, matrix-rich network. We previously reported that pancreatic ductal adenocarcinoma (PDAC) CSCs develop their VM phenotype via two interacting and coordinated factors that support the formation of the VM network: (i) the overexpression of genes for endothelial factors and vascular receptors and (ii) the very high secretion of numerous pro-angiogenic/growth factors. While microenvironmental acidosis (low pHe) is an important driver of tumor metastasis, especially in PDAC, and is a component of the CSC niche, its role in VM and the ion transporters involved remains unknown. As normal stem cell differentiation is regulated by Na⁺/H⁺ exchanger 1 (NHE1)-driven pH, we investigated the role of NHE1 and the intracellular signaling involved in the acidosis-induced VM using a platform of 3D organotypic cultures composed of Matrigel with increasing concentrations of Collagen I. VM was highest on 90% Matrigel:10% Collagen I, representative of an early tumor ECM, and it decreased with increasing concentrations of Collagen I, representative of advanced tumors. In all ECM compositions, VM capacity increased stepwise with pHe acidification, and both basal and acid-stimulated VM were dependent on NHE1 activity. Acidification also decreased resting pHi and increased NHE1 proton extrusion activity, NHE1/ß1 integrin co-expression, and intracellular Ca²⁺. The stimulation of VM by extracellular acidosis depended on the transport of extracellular Ca²⁺ into the cell and the consequent increase in intracellular Ca²⁺. Altogether, these data demonstrate that extracellular acidification triggers cellular mechanisms that upregulate VM to overcome the constraints imposed by ECM composition, thereby permitting VM in ECMs where this phenotype is not expressed and extending the VM phenotype towards the tumor center to further drive metastasis. Full article

Background/Objectives: The escalating crisis of antibiotic resistance and the inherent limitations of conventional antibiotics necessitate the development of innovative therapeutic strategies. Targeted drug delivery (TDD) offers a powerful approach to enhance efficacy, minimize systemic toxicity, and circumvent bacterial resistance. This systematic review aims to evaluate the potential of unique bacterial transport systems (BTSs), surface specific receptors and intracellular enzymes as platforms for TDD via the “Trojan Horse” strategy (THS). Methods: A comprehensive literature review was conducted, focusing on studies that investigated the specificity and mechanisms of BTSs responsible for the uptake of metabolites that are essential for and unique to bacteria. This includes an analysis of transport systems for siderophores, bacteria-specific sugars, cell wall components, D-amino acids, and vitamins. We assessed preclinical and clinical examples of drug conjugates utilizing these pathways, as well as emerging platforms such as bacteriophage-derived proteins, antibody–antibiotic conjugates, and bacterial extracellular vesicles (EVs). Results: BTSs demonstrate high specificity for their cognate substrates, providing effective molecular gateways for TDD of drugs photosensitizers and diagnostic probes in form of conjugates. The siderophore–cephalosporin conjugate cefiderocol represents a clinically validated example, having received FDA approval. Preclinical studies further reveal that conjugates utilizing sugars (e.g., maltose, trehalose) and vitamins (e.g., B12) can significantly enhance antibiotic uptake and activity against both Gram-positive and Gram-negative pathogens, including drug-resistant strains. Emerging platforms like bacteriophage endolysins and engineered EVs show promise for overcoming biological barriers such as bacterial outer membranes and intracellular host niches. Conclusions: The THS leveraging BTSs represents a clinically viable and promising avenue for next-generation antibacterial therapies. Advantages of BTS include overcoming bacterial resistance, such as reduced membrane permeability and efflux pumps, enabling the “revival” of antibiotics that are poorly permeable or toxic, increasing their local concentration at the target site and reducing side effects on host cells. While significant progress has been made, a striking disconnect persists between the hundreds of conjugates demonstrating potent in vitro activity and the limited agent that has achieved clinical use. This in vitro–in vivo gap reflects, in large part, the early stage of this field rather than a fundamental failure. Further research is critically needed not only to identify novel BTSs and optimize drug-linker chemistry, but also to systematically address the translational barriers—including poor pharmacokinetics, immunogenicity, and unexpected toxicity—that have prevented most promising candidates from advancing beyond preclinical evaluation. Full article

Cancer progression is influenced by the dynamic interplay between tumor cells and the surrounding stromal microenvironment. Therapy-induced senescence (TIS) of stromal fibroblasts represents a common outcome of anticancer treatments, contributing to tumor progression through the senescence-associated secretory phenotype (SASP). While SASP cytokines promote cancer malignancy, the contribution of secreted metabolites from senescent cells remains poorly understood. Here, we investigate the role of senescent stromal metabolism in regulating prostate and ovarian cancer cell invasion. Conditioned media (CM) from TIS-induced human prostate (HPFs) and ovarian fibroblasts (HOFs) promote enhanced invasion of cancer cells. Invasion is partially preserved after exposure to boiled CM, suggesting a role for heat-stable metabolic factors. Metabolomic profiling of senescent fibroblasts-derived CM reveals a significant increase in Glutamine (Gln) levels, identifying senescent stromal fibroblasts as a previously unrecognized source of extracellular Gln in the tumor microenvironment (TME). Exposure of cancer cells to senescent CM increases Gln uptake, together with upregulation of the transporter SLC1A5 and increased intracellular Gln. This metabolic adaptation is associated with increased malignant phenotype including epithelial-to-mesenchymal transition (EMT) and stemness features. Extracellular Gln depletion, pharmacological inhibition of glutaminase-1 (GLS1) in cancer cells, or Gln synthetase (GS) silencing in fibroblasts markedly impair senescent fibroblasts CM-induced invasion, EMT markers expression, and stemness features in cancer cells. Stromal-derived Gln is associated with increased cancer cell invasion through activation of a redox-dependent NRF2/ETS1 signaling axis. Analysis of patient-derived transcriptomic datasets further suggests chemotherapy-associated upregulation of Gln metabolism and ETS1 expression. These findings identify senescent stromal-derived Gln as a key metabolic driver of prostate and ovarian cancer aggressiveness and reveal a TIS-associated metabolic vulnerability that could be explored in future preclinical studies. Full article

Protein turnover and extracellular proteolysis continuously generate diverse peptide fragments within biological systems, yet the metabolic and pharmacological implications of these peptides remain incompletely understood. Among these transporters, members of the solute carrier family 15 (SLC15), including peptide transporter 1 (PEPT1/SLC15A1) and peptide transporter 2 (PEPT2/SLC15A2), mediate the proton-coupled uptake of dipeptides, tripeptides, and structurally related compounds across cellular membranes. While these transporters have been extensively studied in the context of intestinal peptide absorption and drug delivery, their potential roles in cancer biology remain incompletely understood. Tumor microenvironments are characterized by extensive proteolysis and dynamic metabolic remodeling, processes that can generate diverse peptide fragments derived from extracellular matrix proteins and intracellular protein turnover. These peptides may accumulate locally and potentially serve as substrates for cellular peptide transport systems. Once internalized through peptide transporters, dipeptides are typically hydrolyzed into free amino acids that can support biosynthetic pathways, energy metabolism, and cellular growth. In addition to their potential metabolic roles, certain endogenous dipeptides have also been reported to influence cellular signaling pathways and redox homeostasis. The broad substrate specificity of peptide transporters has also attracted significant interest in pharmacology because numerous clinically used drugs exploit these transport systems for efficient cellular uptake. This property raises the possibility that peptide transporters may be utilized for transporter-mediated drug delivery strategies, including the development of peptide-modified prodrugs or dipeptide–drug conjugates. In this review, we summarize the molecular characteristics and physiological functions of dipeptide transport systems with a particular focus on the SLC15 transporter family. We then discuss emerging evidence linking peptide transporters to tumor metabolism and the tumor microenvironment. Finally, we highlight current progress and future perspectives in exploiting peptide transport systems for transporter-mediated drug delivery and therapeutic targeting in cancer. Full article