Pancreatitis is a complex inflammatory condition of the pancreas and can be classified into acute pancreatitis (AP) and chronic pancreatitis (CP). The pathogenesis of the disease remains unclear, and effective preventive or therapeutic strategies are currently lacking. Non-coding RNA (ncRNA) regulatory networks consist primarily of miRNAs, lncRNAs, and circRNAs, which precisely regulate gene expression through complex interactions and play a key role in fibrosis and inflammation. In terms of AP, ncRNAs could modulate the activity of pancreatic acinar cells, autophagic flux, inflammatory cell infiltration and the integrity of the intestinal mucosal barrier, which regulates local pancreatic and systemic inflammation. During the progression of CP, ncRNAs mediate the pancreatic persistent inflammation and collagen deposition by regulating the interactions between pancreatic stellate cells and immune cells. ncRNAs serve as promising non-invasive biomarkers for pancreatitis, enabling early diagnosis, severity stratification, complication prediction and differential diagnosis between CP and pancreatic cancer. Therapeutically, ncRNAs represent potential precision intervention targets due to their high regulatability and specificity, although ncRNA-based therapies currently remain at the preclinical stage. Key challenges such as delivery efficiency and targeting specificity must be addressed to facilitate clinical translation. Overall, ncRNAs offer a novel avenue for improving the clinical management of pancreatitis.
Epigenetic regulation is intimately linked to cellular metabolism, enabling environmental and nutritional cues to shape gene expression programs through dynamic modifications of chromatin structure. This metabolism-epigenetics interface is mediated, in part, by the dependence of chromatin-modifying enzymes on key metabolites, including S-adenosylmethionine (SAM), acetyl-CoA, UDP-GlcNAc, and α-ketoglutarate, which serve as substrates or cofactors for DNA and histone modifications. Among these regulators, EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), has emerged as a key mediator linking metabolic state to epigenetic regulation by translating metabolic inputs into changes in chromatin architecture and gene expression. EZH2 governs developmental cell fate through H3K27me3-mediated gene repression and is frequently dysregulated in cancer, where it promotes dedifferentiation, tumor progression, and metabolic reprogramming. Importantly, EZH2 activity is itself modulated by cellular metabolic status through posttranslational modifications, including phosphorylation, acetylation, methylation, ubiquitination, and O-GlcNAcylation, which influence its stability, catalytic activity, and chromatin-binding capacity. These modifications are responsive to nutrient availability and signaling pathways involving glucose, SAM, NAD+, and other metabolic intermediates. Consequently, disruption of this finely tuned regulatory network can contribute to developmental abnormalities, metabolic dysfunction, and oncogenesis. In this review, we examine the molecular mechanisms governing EZH2 regulation and discuss how metabolic control of EZH2 shapes chromatin dynamics, cell fate decisions, and disease pathogenesis. Elucidating how metabolic signals modulate EZH2 activity will advance our understanding of development and disease while uncovering potential therapeutic opportunities to target metabolism-driven epigenetic dysregulation.
Chronic liver disease represents a major global public health challenge, and its malignant progression to hepatocellular carcinoma is the leading cause of death among affected patients. Gut microbiota dysbiosis is a critical driver of this process. As the central hub of the "gut-liver axis," the gut microbiota, when disrupted, compromises the integrity of the intestinal mucosal barrier, promoting the translocation of microbial metabolites, such as lipopolysaccharides and aberrant secondary bile acids, to the liver. In turn, key signaling pathways become activated, including TLR4/NF-κB, Wnt/β-catenin, and PI3K/Akt, sustaining persistent hepatic inflammation and oxidative stress. These pathological processes accelerate the progression from liver fibrosis to cirrhosis, promote genomic instability, and suppress tumor suppressor gene expression, paving the way for the malignant transformation of hepatocytes. Leveraging its holistic regulatory properties, characterized by multi-component, multi-target, and multi-pathway actions, Chinese medicine can intervene at multiple stages of this inflammation-to-cancer cascade by modulating both the structure and function of the gut microbiota. It does so first by enriching beneficial short-chain fatty acid-producing bacteria, such as Lactobacillus and members of the phylum Firmicutes, which helps restore the intestinal mucosal barrier, limit endotoxin translocation, and alleviate hepatic inflammation and fibrosis. In parallel, by normalizing bile acid metabolism and reestablishing gut microbial homeostasis, Chinese medicine counteracts the development of a tumor-permissive microenvironment marked by immune suppression and DNA damage in hepatocytes induced by microbial metabolites. At the same time, it enhances anti-tumor immune responses mediated by CD8+ T cells and other immune effectors. Drawing on evidence from multi-omics analyses and clinical studies, this review examines the core mechanisms and recent advances regarding how Chinese medicine monomers and formulations modulate the gut microbiota to impede the progression of chronic liver disease to HCC. It highlights gut microbiota dysbiosis as a key driver of hepatocarcinogenesis and highlights the therapeutic potential of targeted microbiota regulation by Chinese medicine, providing a conceptual foundation and strategic approaches for the precision prevention and treatment of hepatocellular carcinoma.
Residual disease after cytoreductive surgery is a dominant, surgeon-modifiable determinant of outcome in advanced ovarian cancer, yet white-light inspection cannot reliably identify microscopic implants, plaque-like deposits, or therapy-altered fibrotic foci across complex peritoneal surfaces. Intraoperative molecular imaging aims to close this visibility gap by translating tumor-associated biology into real-time signal that can prompt additional resection, direct sampling, and support intraoperative decision-making. Across probe classes, folate receptor-α-targeted agents represent the most clinically mature approach, while activatable tracers and multimodal platforms are expanding capabilities beyond superficial visualization. However, improved detection alone does not establish patient benefit. We therefore frame molecular guidance as a workflow intervention and organize evidence along a clinically oriented hierarchy-lesion detection, decision impact, and patient outcomes-highlighting the need for standardized acquisition/quantification and pathology-linked validation. We propose pragmatic, trial-compatible definitions for pathology-confirmed completeness and prespecified molecular field clearance, and discuss how AI-assisted interpretation, multimodality, and radionuclide-enabled strategies could strengthen reproducibility and extend management toward microscopic residual disease.
Prostate cancer is among the top causes of cancer-related mortality in men, according to the latest data from GLOBOCAN, driven primarily by androgen receptor signaling and initially treated with androgen deprivation therapy. However, most patients progress to a resistant state characterized by mechanisms such as receptor amplification, mutations, splice variants, and activation of alternative pathways. This review summarizes the key molecular drivers of resistance and evaluates emerging invasive biomarkers with potential clinical utility, though most remain insufficiently validated. It also outlines current and emerging therapeutic strategies to overcome resistance, highlighting ongoing challenges in clinical implementation.
Peripheral nerve repair remains a major clinical challenge due to limited functional recovery and the lack of effective therapeutic options. Extracellular vesicles (EVs) have emerged as potential mediators of nerve regeneration due to their roles in cell-to-cell communication and the delivery of diverse bioactive molecules. The regenerative potential of EVs largely depends on the type of cell they originate from, which determines their molecular cargo and therapeutic potential. This review provides a comprehensive and focused analysis on the source-specific composition of EVs, and how different EVs distinctly influence neuroprotective, immunomodulatory, and neuroregenerative properties with direct relevance to peripheral nerve injury (PNI). We also highlight current evidence on how EVs modulate nerve repair pathways and discuss the implications of their source-specific content in optimizing EV-based therapies alongside recent technological advances for PNI. By highlighting key differences in regenerative-associated signaling, this review provides insight into optimizing EV-based therapies for PNI and outlines prospects for clinical application.
Breast cancer (BC) is estimated to be around 2.3 million new cases and 670 000 deaths in 2020 resulting it into the most frequent cancer globally and ranks fifth among mortalities. Numerous studies have established the link between BC and microRNAs (miRNAs), which are endogenous non-protein-coding master regulators that modulate genetic expressions and influences many physiological and pathological cellular processes. In addition, hypoxia, which also consequently leads to cancer, is a pivotal driver of biological behaviour and malignant traits of cancer cells and eventually tumour cell survival. Hypoxia and hypoxia-inducible factors (HIFs) further regulates the miRNAs expression and promotes invasion and metastasis via increased invasive, migratory, and intravasation properties of the cancer cell, which initiates the metastatic process. In subsequent stages of metastasis, cancer cells navigate immune escape, vascular extravasation, metabolic reprogramming, and tumour-stromal crosstalk at the distant tissue site. Hypoxia dysregulates cancer metabolism post-transcriptionally through miRNAs, promoting glycolysis and fatty acid metabolism by inducing the expression of genes such as GLUT1, SCD, lipidome, and glycolytic enzyme biosynthesis. Hypoxia, on the other hand, also regulates immunogenic reprogramming by circumventing immunosurveillance, perpetuating cell survival and progression via hampering CD-47, PD-L1 markers and T-cell activation. Another process of cancer known as programmed cell death types I and II also involves a complex intricate protein mediated by HIF-1α. Hypoxia-mediated drug resistance influence drug therapeutic effect via altering transporter flux, drug targets, and inactivate of apoptotic pathways. In this review, we are focusing on understanding the clinical implications of hypoxia-driven miRNAs in BC diagnosis and prognosis. Therapeutic landscape for these molecules remains largely untapped, resulting into conducting more research in this field for harbouring potential translational discoveries in the diagnosis, prognosis and therapeutics for BC.
Cancer transcends a local disease by engaging in systemic crosstalk with the host's physiology. This review redefines the vagus nerve as a central bioelectric processor within a dynamic brain-body-tumor homeostatic network, orchestrating a complex biological dialogue between them. We synthesize evidence illustrating its specialized architecture for encoding tumor microenvironment signals across metabolic, immune, and endocrine interfaces. Functioning as a dynamic, context-dependent integrator, it maintains systemic homeostasis while paradoxically being susceptible to hijacking by tumors, underscoring its dual role as both guardian and accomplice in cancer progression. This mechanistic framework paves the way for novel therapeutic reprogramming strategies. We explore the potential of precision bioelectronic neuromodulation, pharmacological interception of neural signaling, and behavioral interventions to "hack" this dialogue, aiming to enhance anti-tumor defenses, alleviate cancer-related symptoms, and synergize with conventional therapies. Future success hinges on deciphering the vagal neural code and developing personalized, ethically sound applications.
The rising global burden of cancer and diabetes mellitus, particularly type 2 diabetes (T2DM), underscores a critical need for integrated therapeutic strategies. Epidemiological studies reveal a compelling bidirectional association between these diseases, with T2DM increasing cancer risk and adversely affecting cancer prognosis. Shared pathophysiological mechanisms including insulin/IGF-1 signaling, chronic low-grade inflammation, oxidative stress, and metabolic reprogramming serve as potential therapeutic convergence points. This review explores the mechanistic and clinical basis for dual-targeting strategies that address both malignancy and metabolic dysfunction simultaneously. Key molecular intersections include the PI3K/Akt/mTOR and AMPK pathways, which are central to cell proliferation, survival, and glucose metabolism. Pharmacological agents like metformin, SGLT2 inhibitors, and statins demonstrate promising anticancer effects in addition to glycemic control, while biologics such as canakinumab and tocilizumab modulate inflammatory processes relevant to both disease states. Natural compounds including curcumin, resveratrol, and berberine exhibit dual benefits via antioxidant, anti-inflammatory, and metabolic pathways. The review critically evaluates preclinical studies, retrospective cohort analyses, and clinical trial data supporting the repurposing of anti-diabetic agents for oncology indications. Despite mixed outcomes in large-scale trials, evidence suggests biomarker-based patient selection may enhance therapeutic efficacy. Moreover, emerging paradigms including immunometabolism, gut microbiota modulation, and gene-based interventions offer promising frontiers for integrated care. Ultimately, dual-targeting strategies represent an emerging and promising therapeutic framework for managing patients with overlapping cancer and metabolic disease, with potential to optimize outcomes, reduce therapy-related toxicities, improve long-term survival. Future research must prioritize biomarker-guided precision therapies, multidisciplinary management and the inclusion of metabolic parameters in oncology trial designs.
Diabetes mellitus (DM) is a significant risk factor for several cancers, particularly cancers of the liver, pancreas, and endometrium. This review aims to understand the connections between diabetic pathophysiology and cancer biology. We synthesize how core metabolic disturbances—hyperinsulinemia, hyperglycemia, and inflammation—promote tumorigenesis by dysregulating canonical oncogenic pathways such as IGF-1 signaling, DNA damage repair, and immunometabolism. Subsequently, we focus on how key molecular integrators—such as p38 MAPK, Wnt/β-catenin, and the AGEs-RAGE axis—mediate metabolic stress to confer proliferative and invasive advantages to tumor cells. However, a direct translational application of these mechanisms, particularly in the context of repurposing antidiabetic drugs for cancer therapy, remains challenging due to inconsistent clinical outcomes. To address this gap, we suggest that a fundamental shift in approach is required. We propose that future research must move beyond simple pathway categorization and instead utilize spatial analysis techniques to reveal how diabetic metabolites reshape the tumor microenvironment (TME). By integrating single-cell and spatial omics technologies, the field can begin to map the precise cellular niches within tumors where diabetic metabolites exacerbate malignant progression and foster treatment resistance. This perspective is essential for developing targeted strategies to mitigate cancer risk and improve outcomes for the expanding population of patients with DM and cancer.
The eye maintains vision through a distinctive immune privilege, utilizing physical barriers and active immunosuppression mediated by molecules such as FasL and PD-L1, as well as cells, including regulatory T cells and RPE cells. The emergence of sight-threatening immune-mediated ocular diseases, including non-infectious uveitis, signifies a significant disruption of this tolerance. This review analyzes the role of viral triggers and genetic predisposition in inducing immunological failure, while emphasizing the development of targeted therapeutic strategies.Viruses induce autoimmunity through molecular mimicry (Rotavirus peptides cross-reacting with retinal S-antigen), bystander activation, and active immune suppression (CMV inhibiting RPE cell IDO1 activity). HLA alleles, especially HLA-A29 (Birdshot Chorioretinopathy) and HLA-B27 (acute anterior uveitis), as well as non-MHC genes like NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and AIRE, greatly increase the risk of genetic disorders.Treatment is progressing towards precision medicine, with targeted biologics like the IL-6 receptor inhibitor Tocilizumab being key strategies. Moreover, AAV-mediated gene therapy that expresses immunosuppressive molecules such as HLA-G demonstrates promise for the restoration of long-term tolerance in preclinical models, facilitating the development of advanced future strategies.
Traditionally, mammalian spermatozoa have been viewed as transcriptionally and translationally inert cells that merely deliver paternal DNA to the oocyte. However, the advent of high-throughput RNA sequencing and mass-spectrometry-based proteomics has fundamentally revised this paradigm. Mature sperm are now known to harbor a diverse and dynamic repertoire of coding and non-coding RNAs-including mRNAs, lncRNAs, miRNAs, piRNAs, tsRNAs and circRNAs-as well as a rich proteome and specialized ribosomes that together support tightly regulated post-testicular functions. These RNA and protein cargos originate from spermatogenesis, epididymal extracellular vesicle-mediated transfer, and possibly limited de novo transcription, and are further shaped by environmental and lifestyle factors. Functionally, sperm RNAs and translational activities contribute to sperm maturation, motility, capacitation, fertilization, and early embryonic development, and are implicated in intergenerational epigenetic inheritance. Comparative transcriptomic and proteomic studies across humans and livestock demonstrate that specific RNA and protein signatures distinguish high-from low-fertility males, highlighting their potential as biomarkers for male fertility assessment and as companion tools for assisted reproduction. Emerging evidence that cytoplasmic and mitochondrial translation can occur during capacitation further underscores that spermatozoa are dynamic cells capable of context-dependent protein synthesis. This review synthesizes current advances in sperm transcriptional and translational biology, with a focus on the origin and regulation of sperm RNAs, the role of specialized ribosomes and translation factors, environmental modulation of these processes, and the translational potential of sperm RNA and protein profiles as diagnostic, prognostic, and therapeutic targets in male reproductive medicine.
Inherited retinal diseases (IRDs) are a genetically diverse group of disorders characterized by progressive photoreceptor degeneration, leading to vision loss and blindness. With over 320 associated genes and significant phenotypic variability, effective treatment remains challenging. Recent advances in genome editing, particularly CRISPR/Cas-based technologies, have revolutionized therapeutic approaches by enabling precise and customizable DNA and RNA editing. This review explores the application of various CRISPR strategies—such as gene knockout via non-homologous end joining (NHEJ), exon skipping using dual-sgRNAs, homology-directed repair (HDR), base editing (BE), prime editing (PE), RNA editing with Cas13, and epigenetic modulation through CRISPRa/i—in preclinical models of IRDs. Emphasis is placed on allele-specific targeting, gene-agnostic approaches, and mutation-independent strategies to address dominant and recessive forms of disease. We also highlight recent clinical milestones, including the first human trial using CRISPR gene editing for CEP290-associated Leber congenital amaurosis. Finally, we discuss critical challenges, including delivery constraints, immune responses, and off-target effects, along with emerging solutions such as engineered Cas variants, split-intein systems, and advanced off-target detection methods. Together, these advances underscore the transformative potential of CRISPR technologies in treating IRDs and lay the foundation for future clinical translation.
Modern lifestyle patterns, characterized by high-calorie diets and sedentary behaviour, have driven a global surge in obesity, which is a primary driver of insulin resistance (IR) and type 2 diabetes mellitus (T2D). Initially, pancreatic β-cells adapt to IR by increasing proliferation, neogenesis, and insulin secretion to maintain normoglycemia. Also, a prolonged exposure to genetic and environmental stress compromises the β-cell functioning and survival, leading to chronic hyperglycaemia. Beyond its central role in T2D, IR and its metabolic hallmarks, such as hyperinsulinemia, hyperglycaemia, dyslipidaemia, and chronic inflammation, are increasingly linked to heightened cancer risk and adverse outcomes in breast, colon, pancreatic, liver, bladder, and endometrial cancers. Aberrant insulin/IGF signalling, enhanced oxidative stress, inflammatory cytokines, and metabolic reprogramming are key molecular mediators of cancer progression. At the organelle level, both endoplasmic reticulum (ER) and mitochondria, and their functional crosstalk via mitochondria-associated membranes (MAMs), are critical in IR. However, a disruption in ER homeostasis might trigger ER stress and activate the unfolded protein response (UPR), culminating in a cellular adaptive mechanism. A dysregulation in this response contributes to lipid accumulation, inflammation, impaired insulin biosynthesis, and β-cell apoptosis. Simultaneously, altered MAM integrity disrupts calcium signalling, mitochondrial metabolism, and ER-mitochondria crosstalk, further aggravating IR across tissues, including liver, muscle, β-cells, and brain. Thus, UPR dysregulation and MAM perturbations represent a mechanistic nexus linking IR, T2D, and cancer. Understanding how these processes intersect might help in uncovering promising therapeutic avenues targeting ER stress, restoring MAM integrity, modulating UPR signalling, and thereby improving insulin sensitivity, mitigating metabolic disease and oncogenic risk.
The liver-brain axis (LBA) represents a sophisticated, dynamic bidirectional communication network that is fundamental to systemic metabolic and homeostatic regulation. This review synthesizes current understanding of the LBA as an integrated, multi-layered system encompassing neural, humoral, immune-inflammatory, metabolic, and circadian signaling pathways. Moving beyond organ-centric perspectives, we detail how hepatic-derived factors—including hepatokines, metabolites, and extracellular vesicles—directly influence cerebral function, while central neural and neuroendocrine outputs dynamically modulate hepatic physiology. Dysregulation within this network underlies a broad spectrum of pathologies, from metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes to neurodegenerative disorders, psychiatric conditions, and hepatocellular carcinoma. We further explore emerging therapeutic strategies aimed at recalibrating this axis, emphasizing innovative approaches such as neuromodulation, chrononutrition, exercise, natural products, and precision gene editing. By adopting a systems-level perspective, this review advocates for a paradigm shift from isolated organ treatment to network-based medicine, highlighting the therapeutic potential of recalibrating inter-organ communication.
Type 2 diabetes mellitus (T2DM) contributes significantly to the development and progression of cancers of the female reproductive tissues, particularly endometrial, ovarian, and breast. Hallmarks of T2DM, such as hyperinsulinemia, insulin resistance, and chronic low-grade inflammation, disrupt endocrine and metabolic homeostasis, promoting carcinogenesis through enhanced mitogenic signaling, hormonal dysregulation, and immune activation. T2DM can alter ovarian, endometrial, and mammary physiology by affecting estrogen/progesterone receptor activity, stromal remodeling, and specialized cell function. Furthermore, give the fluctuations in a woman's hormonal levels and reproductive status, the presence of excess weight and T2DM may have altering risks depending on the lifecycle. These effects are exacerbated by adipose-derived cytokines and leptin resistance, further amplifying estrogens' bioavailability and pro-inflammatory signaling. Endometrial cancer risk is nearly doubled in diabetic women, independent of body mass index, with hyperglycemia inducing PI3K/AKT/mTOR and NF-κB pathway activation, reduced sex hormone-binding globulin (SHBG) levels, and upregulation of estrogen receptor signaling. Ovarian cancer in diabetic patients is associated with more aggressive histological subtypes, advanced-stage presentation, and poorer survival, likely driven by Insulin-like growth factor 1 (IGF-1) signaling, oxidative stress, and impaired treatment response. Similarly, T2DM increases the risk and worsens outcomes in breast cancer via enhanced expression, AGE-RAGE interactions, and estrogen-independent ERα activation. Herein, we synthesize current epidemiological evidence and mechanistic insights to delineate the multifaceted relationship between T2DM and these cancers. Despite increased risk, diabetic women often face underdiagnosis due to suboptimal screening practices. As T2DM prevalence rises globally, tailored cancer prevention and treatment strategies for diabetic populations are urgently needed. Metformin has shown robust benefits in reducing T2DM-related complications and potential in the antineoplastic setting. This review underscores the endocrine and inflammatory mechanisms linking T2DM to cancers of the female reproductive system and advocates for integrated clinical protocols that include early screening and individualized management in diabetic women.
Pathogenic nonsense variants introduce premature termination codons (PTCs) into gene coding sequences, resulting in truncated, typically nonfunctional proteins. Translational readthrough has emerged as a promising therapeutic strategy for genetic diseases caused by nonsense variants. Small molecules, known as translational readthrough-inducing drugs (TRIDs), act as therapeutic agents, by allowing the translation machinery to suppress nonsense variants. TRIDs induce ribosomes to bypass aberrant stop codons favoring the incorporation of near-cognate amino acids at PTC sites. This restores the synthesis of full-length, potentially functional proteins. As TRIDs function on the mRNA level, they enable the expression of various heterogeneous isoforms of the target gene, and moreover the size of the gene is not relevant. This paves the way for the treatment of patients carrying PTCs in genes with many splice variants and in large genes. Although the efficacy of TRIDs varies across genes and PTCs, one TRID could potentially be applied for different disease-causing genes, making the strategy particularly attractive from an economic perspective for rare and ultra-rare disorders. Here we describe basic aspects of translational readthrough, TRIDs currently under investigation for the treatment of Inherited Retinal Disorders and discuss the current needs to improve translational readthrough therapy. Finally, we describe a “pipeline” to identify the best TRIDs for a specific gene/PTC, which could provide a customized readthrough approach for each patient with a PTC-caused disease.
Obesity and type II diabetes mellitus (T2DM) are intricately linked to elevated cancer risk. Protein Kinase D (PKD) isoforms (PKD1, PKD2, and PKD3) have emerged as pivotal mediators at the centre of metabolic and oncogenic signalling. This review discusses isoform-specific roles of PKDs in the pathophysiology of both metabolic disorders and tumour progression. PKD1 exhibits a context-dependent dual role in cancer, acting as a tumour suppressor by reinforcing epithelial adhesion and restricting invasion in several carcinomas, yet exerting pro-tumorigenic effects in specific tissues such as the pancreas and skin. Metabolically, PKD1 supports insulin secretion in pancreatic β cells while promoting adipocyte lipogenesis and suppressing thermogenesis, mechanisms that contribute to systemic insulin resistance and may prime the tumour microenvironment. PKD2 promotes tumour progression through sustained hypoxia signalling, matrix remodelling, and immune evasion, driven by its regulation of HIF-1α, Snail, β-catenin, and PD-L1. PKD3 facilitates oncogenic proliferation and metabolic rewiring, particularly enhancing glycolysis via the p65/PFKFB3 axis and modulating insulin/glucagon signalling in hepatocytes. Obesity- or diabetes-related factors, such as diacylglycerol, leptin, and pro-inflammatory cytokines, enhance PKD signalling across tissues, reinforcing its role in connecting metabolic disorders to cancer. These findings highlight PKD isoforms as potential therapeutic targets, particularly in cancer settings where metabolic dysfunction plays a contributing role. While current PKD inhibitors lack isoform specificity, future therapeutic strategies focused on PKD2 and PKD3 modulation may offer selective control over invasion, immune evasion, and metabolic reprogramming in metabolically comorbid cancer patients.
