Therapeutic Opportunities Research Articles

The Roles of Myeloid Cells in Breast Cancer Progression.

This chapter reviews tumor-associated myeloid cells, including macrophages, neutrophils, and other innate immune cells, and their multifaceted roles in supporting breast cancer progression and metastasis. In primary tumors, myeloid cells play key roles in promoting tumor epithelial-mesenchymal transition (EMT) and invasion. They can facilitate intravasation (entry into the bloodstream) and colonization, disrupting the endothelial cell layer and reshaping the extracellular matrix. They can also stimulate angiogenesis, suppress immune cell responses, and enhance cancer cell adaptability. In the bloodstream, circulating myeloid cells enable the survival of disseminated tumor cells via immunosuppressive effects and physical shielding. At the metastatic sites, they prime the premetastatic niche, facilitate tumor cell extravasation, and support successful colonization and outgrowth. Mechanistically, myeloid cells enhance cancer cell survival, dormancy escape, proliferation, and mesenchymal-epithelial transition (MET). Nonetheless, substantial gaps in our understanding persist regarding the functional and spatiotemporal diversity, as well as the evolutionary patterns, of myeloid cells during metastatic progression. Myeloid cell plasticity and differential responses to therapies present key barriers to successful treatments. Identifying specific pro-tumoral myeloid cell subpopulations and disrupting their interactions with cancer cells represent promising therapeutic opportunities. Emerging evidence suggests combining immunomodulators or stromal normalizers with conventional therapies could help overcome therapy-induced immunosuppression and improve patient outcomes. Overall, further elucidating myeloid cell heterogeneity and function throughout the process of breast cancer progression and metastasis will enable more effective therapeutic targeting of these critical stromal cells.

Spliced exon9 ADRM1 promotes liver oncogenicity via selective degradation of tumor suppressor FBXW7.

The ubiquitin receptor ADRM1/Rpn13 governs the specificity of eukaryotic protein degradation. By SMRT sequencing, we first discovered a novel spliced variant of ADRM1 with a skipped exon 9, termed ADRM1-ΔEx9, in human hepatocellular carcinoma (HCC). This study aimed to elucidate this novel ubiquitin receptor's underlying biology and clinical implications in HCC. The role of ADRM1-ΔEx9 in early liver carcinogenesis was studied using human liver-derived non-tumoral organoids and a murine model with hydrodynamic in vivo transfection. ADRM1-ΔEx9 biology in HCC and its potential as a biomarker for predicting Olaparib response were investigated using patient-derived tumor organoids and xenograft models. The underlying mechanism was delineated using the Proteome Profiler Human Ubiquitin Array. ADRM1-ΔEx9, not its full-length counterpart, conferred human liver organoids with pro-survival advantages and a more profound tumor formation in a hydrodynamic transfected murine model. Functional knockdown resulted in spontaneous apoptosis in cell lines and patient-derived organoids, highlighting a pivotal role for ADRM1-ΔEx9 in HCC oncogenicity. Mechanistically, the shortened C-terminus of ADRM1-ΔEx9 signified a specific deubiquitinase partner BAP1 and navigated proteasome specificity. The new exon 8-10 fusion in ADRM1-ΔEx9 created a de novo binding to tumor suppressor protein FBXW7, resulting in its selective proteasome-mediated degradation. The loss of FBXW7 protein in ADRM1-ΔEx9 expressing tumors underscores their sensitivity to PARP inhibitor Olaparib. Notably, findings on ADRM1-ΔEx9 in primary HCC tumors denote its overexpression in a subgroup of patients with inferior survival and a window of therapeutic opportunity through its synthetic lethality association with Olaparib. ADRM1-ΔEx9 redirects ubiquitin proteasome specificity to degrade the tumor suppressor protein FBXW7 selectively. This promotes HCC tumor formation and provides a synthetic lethal link for PARPi therapy. Reduced tumor suppressor protein FBXW7 expression is pivotal in HCC pathogenesis and other liver diseases. However, the regulatory mechanism governing FBXW7 protein expression remains elusive. Herein, we unveil a non-canonical spliced isoform of the ubiquitin receptor ADRM1 that selectively degrades FBXW7 protein, thereby promoting the premalignant transformation of hepatic cells and conferring growth advantages to HCC tumors. Furthermore, our results demonstrate that ADRM1-ΔEx9-expressing HCC tumors exhibited sensitivity to Olaparib in a dose-dependent manner, implicating the potential use of Olaparib in targeting ADRM1-ΔEx9-driven HCC growth.

When "loss-of-function" means proteostasis burden: Thinking again about coding DNA variants.

Each human genome has approximately 5 million DNA variants. Even for complete loss-of-function variants causing inherited, monogenic diseases, current understanding based on gene-specific molecular function does not adequately predict variability observed between people with identical mutations or fluctuating disease trajectories. We present a parallel paradigm for loss-of-function variants based on broader consequences to the cell when aberrant polypeptide chains of amino acids are translated from mutant RNA to generate mutated proteins. Missense variants that modify primary amino acid sequence, and nonsense/frameshift variants that generate premature termination codons (PTCs), are placed in context alongside emergent themes of chaperone binding, protein quality control capacity, and cellular adaptation to stress. Relatively stable proteostasis burdens are contrasted with rapid changes after induction of gene expression, or stress responses that suppress nonsense mediated decay (NMD) leading to higher PTC transcript levels where mutant proteins can augment cellular stress. For known disease-causal mutations, an adjunctive variant categorization system enhances clinical predictive power and precision therapeutic opportunities. Additionally, with typically more than 100 nonsense and frameshift variants, and ∼10,000 missense variants per human DNA, the paradigm focuses attention on all protein-coding DNA variants, and their potential contributions to multimorbid states beyond classically designated inherited diseases. Experimental testing in clinically relevant systems is encouraged to augment current atlases of protein expression at single-cell resolution, and high-throughput experimental data and deep-learning models that predict which amino acid substitutions generate enhanced degradative burdens. Incorporating additional dimensions such as pan-proteome competition for chaperones, and age-related loss of proteostasis capacity, should further accelerate health impacts.

Role of Fungi in Tumorigenesis: Promises and Challenges.

The mycobiome plays a key role in the host immune responses in homeostasis and inflammation. Recent studies suggest that an imbalance in the gut's fungi contributes to chronic, noninfectious diseases such as obesity, metabolic disorders, and cancers. Pathogenic fungi can colonize specific organs, and the gut mycobiome has been linked to the development and progression of various cancers, including colorectal, breast, head and neck, and pancreatic cancers. Some fungal species can promote tumorigenesis by triggering the complement system. However, in immunocompromised patients, fungi can also inhibit this activation and establish life-threatening infections. Interestingly, the interaction of the fungi and bacteria can also induce unique host immune responses. Recent breakthroughs and advancements in high-throughput sequencing of the gut and tumor mycobiomes are highlighting novel diagnostic and therapeutic opportunities for cancer. We discuss the latest developments in the field of cancer and the mycobiome and the potential benefits and challenges of antifungal therapies.

FT-4202, a selective pyruvate kinase R activator for sickle cell disease

Anemia in patients with sickle cell disease (SCD) increases 2,3-diphosphoglycerate (2,3-DPG), decreasing hemoglobin–oxygen (Hb-O2) affinity to improve oxygen offloading and promote hemoglobin polymerization (sickling) of red blood cells (RBCs). We report the discovery of FT-4202, an investigational, selective pyruvate kinase type-R (PKR) activator with a multimodal mechanism of action and potential to increase ATP and decrease 2,3-DPG, resulting in increased Hb-O2 affinity, decreased Hb polymerization, and improved RBC health. FT-4202 was identified via structure-enabled lead optimization medicinal chemistry using X-ray crystallography, molecular modeling, and thermal shift assays. FT-4202, an allosteric PKR activator, stabilizes the tetrameric enzyme and increases PKR activity in human and mouse RBCs in vitro. Seven-day oral administration of FT-4202 in Berkeley SCD mice reduced 2,3-DPG, increased Hb-O2 affinity, and reduced RBC sickling versus control. There were no adverse in vitro safety findings. FT-4202 offers a therapeutic opportunity to modify the course of SCD.

Pathophysiology of the Skin in Type 1 and Type 2 Diabetes and Emerging Therapeutic Opportunities

Pathophysiology of the Skin in Type 1 and Type 2 Diabetes and Emerging Therapeutic Opportunities

The Clinical Utility of the Ocrelizumab for the Patients with Multiple Sclerorsis

Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory disease of the central nervous system, primarily affecting young adults, and is characterized by demyelination and neurodegeneration. Although several disease-modifying therapies (DMTs) are available in Korea, patients who experience inadequate responses or disease progression continue to require more effective and safer therapeutic options. Ocrelizumab, a humanized monoclonal antibody targeting CD20 of B cells, has shown high efficacy in both relapsing forms of multiple sclerosis and primary progressive multiple sclerosis patients. It was approved by the Food and Drug Administration in 2017 and approved by Ministry of Food and Drug Safety Korea in 2024. Clinical trials such as the OPERA and ORATORIO studies demonstrated that ocrelizumab significantly reduced relapse rates, disability progression, and magnetic resonance imaging lesions compared to interferon beta 1a or placebo. Real-world data further supports its clinical value, showing similar or superior efficacy to other high-efficacy DMTs. Long-term safety profile of ocrelizumab remains favorable, with manageable risks such as infections, particularly lower respiratory tract and urinary tract infections. This review discusses the clinical value of ocrelizumab in the treatment of multiple sclerosis, its potential as a tolerable high efficacy treatment option for patients in need of more effective therapies. Based on the clinical evidence, ocrelizumab offers a promising therapeutic opportunity for Korean MS patients, especially those with high disease activity, and is expected to become an essential part of MS treatment strategies worldwide.

Genomic profiling reveals SMARCA4 mutations are associated with shorter overall and intracranial progression free survival in melanoma brain metastasis patients.

Melanoma brain metastases (MBMs) are a common, lethal complication of metastatic melanoma. Despite improvements in treatments, subsets of MBM patients experience rapid decline, and few prognostic biomarkers have been identified. An improved understanding of the molecular features specifically associated with MBM overall survival (OS) and intracranial progression free survival (PFS) could facilitate the development of more effective clinical management strategies. We established an initial cohort of 102 MBMs, 970 unmatched melanoma extracranial metastases (ECMs), and 569 unmatched melanoma primaries with available targeted exome sequencing data covering 182 genes and a validation cohort of 50 MBMs with SMARCA4 genomically profiled. Kaplan-Meier analysis, log-rank test, and Cox proportional hazards model were used to evaluate associations between pathogenic genomic alterations and OS and intracranial PFS. We evaluated 14 MBMs and 19 ECMs with paired RNA sequencing and whole exome sequencing data to identify genotype-transcriptome correlations. Of 43 genes significantly mutated amongst MBMs, only pathogenic mutations in SMARCA4 significantly associated with shorter OS and intracranial PFS on univariable and multivariable analyses in MBM patients but not from first ECM or primary tumor diagnosis. SMARCA4 mutations significantly associated with enrichment of oxidative phosphorylation (OXPHOS) and depletion of immune signaling gene sets. Pathogenic SMARCA4 mutations independently predict an association with shorter OS and intracranial PFS in MBM patients and associate with expression of pathways known to mediate melanoma virulence. These findings add to our understanding of MBM pathogenesis and suggest their potential use as prognostic biomarkers and possible therapeutic opportunities.

Insights into PI3K/AKT signaling in B cell development and chronic lymphocytic leukemia

The phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) signaling pathway is a central regulator of B cell biology, influencing survival, proliferation, metabolism, and immune responses. This Review explores how in both normal and malignant B cells, signaling operates within a finely tuned “comfort zone”, where appropriate levels support cell growth and survival. This comfort zone is dynamically modulated by the developmental stage, costimulatory signals, and the duration, magnitude, and subcellular localization of signaling events. In chronic lymphocytic leukemia, aberrant PI3K/AKT activation drives disease progression and resistance to therapy. Notably, deviations from the comfort zone—whether through excessive hyperactivation or insufficient signaling—can trigger cell death, presenting therapeutic opportunities. Signaling thresholds influence normal B cell development and chronic lymphocytic leukemia pathogenesis, including mechanisms of immune escape and Richter's transformation, an aggressive progression from chronic lymphocytic leukemia. Therapeutic strategies targeting PI3K/AKT are evaluated, with a focus on challenges such as toxicity. By understanding the nuanced modulation of the signaling comfort zone, we can refine therapies to selectively eliminate leukemic cells while preserving normal B cell function, offering new hope for improved treatment outcomes.

Deciphering a profiling based on multiple post-translational modifications functionally associated regulatory patterns and therapeutic opportunities in human hepatocellular carcinoma

BackgroundPosttranslational modifications (PTMs) play critical roles in hepatocellular carcinoma (HCC). However, the locations of PTM-modified sites across protein secondary structures and regulatory patterns in HCC remain largely uncharacterized.MethodsTotal proteome and nine PTMs (phosphorylation, acetylation, crotonylation, ubiquitination, lactylation, N-glycosylation, succinylation, malonylation, and β-hydroxybutyrylation) in tumor sections and paired normal adjacent tissues derived from 18 HCC patients were systematically profiled by 4D-Label free proteomics analysis combined with PTM-based peptide enrichment.ResultsWe detected robust preferences in locations of intrinsically disordered protein regions (IDRs) with phosphorylated sites and other site biases to locate in folded regions. Integrative analyses revealed that phosphorylated and multiple acylated-modified sites are enriched in proteins containing RRM1 domain, and RNA splicing is the key feature of this subset of proteins, as indicated by phosphorylation and acylation of splicing factor NCL at multiple residues. We confirmed that NCL-S67, K398, and K646 cooperate to regulate RNA processing.ConclusionTogether, this proteome profiling represents a comprehensive study detailing regulatory patterns based on multiple PTMs of HCC.

TH301 Emerges as a Novel Anti-Oncogenic Agent for Human Pancreatic Cancer Cells: The Dispensable Roles of p53, CRY2 and BMAL1 in TH301-Induced CDKN1A/p21CIP1/WAF1 Upregulation.

Background: Pancreatic Ductal Adeno-Carcinoma (PDAC) is a highly aggressive cancer, with limited treatment options. Disruption of the circadian clock, which regulates key cellular processes, has been implicated in PDAC initiation and progression. Hence, targeting circadian clock components may offer new therapeutic opportunities for the disease. This study investigates the cytopathic effects of TH301, a novel CRY2 stabilizer, on PDAC cells, aiming to evaluate its potential as a novel therapeutic agent. Methods: PDAC cell lines (AsPC-1, BxPC-3 and PANC-1) were treated with TH301, and cell viability, cell cycle progression, apoptosis, autophagy, circadian gene, and protein expression profiles were analyzed, using MTT assay, flow cytometry, Western blotting, and RT-qPCR technologies. Results: TH301 proved to significantly decrease cell viability and to induce cell cycle arrest at the G1-phase across all PDAC cell lines herein examined, especially the AsPC-1 and BxPC-3 ones. It caused dose-dependent apoptosis and autophagy, and it synergized with Chloroquine and Oxaliplatin to enhance anti-oncogenicity. The remarkable induction of p21 by TH301 was shown to follow clock- and p53-independent patterns, thereby indicating the critical engagement of alternative mechanisms. Conclusions: TH301 demonstrates significant anti-cancer activities in PDAC cells, thus serving as a promising new therapeutic agent, which can also synergize with approved treatment schemes by targeting pathways beyond circadian clock regulation. Altogether, TH301 likely opens new therapeutic windows for the successful management of pancreatic cancer in clinical practice.

A multiparametric screen uncovers FDA-approved small molecules that potentiate the nuclear mechano-dysfunctions in ATR-defective cells

Targeting nuclear mechanics is emerging as a promising therapeutic strategy for sensitizing cancer cells to immunotherapy. Inhibition of the mechano-sensory kinase ATR leads to mechanical vulnerability of cancer cells, causing nuclear envelope softness and collapse and activation of the cGAS-STING-mediated innate immune response. Finding novel compounds that interfere with the non-canonical role of ATR in controlling nuclear mechanics presents an intriguing therapeutic opportunity. We carried out a multiparametric high-content screen to identify small molecules that affect nuclear envelope shape and to uncover novel players that could either ameliorate or further compromise the nuclear mechanical abnormalities of ATR-defective cells. The screen was performed in HeLa cells genetically depleted for ATR. Candidate hits were also tested in combination with the chemical inhibition of ATR by AZD6738, and their efficacy was further validated in the triple-negative breast cancer cell lines BT549 and HCC1937. We show that those compounds enhancing the abnormal nuclear shape of ATR-defective cells also synergize with AZD6738 to boost the expression of interferon-stimulated genes, highlighting the power of multiparametric screens to identify novel combined therapeutic interventions targeting nuclear mechanics for cancer immunotherapy.

Prototype of Implant for Nitric Oxide Release Controlled byInfrared Radiation in Therapeutic Window.

Local therapeutic action and targeted drug release are promising approaches compared to traditional systemic drug administration. This is especially relevant for nitric oxide (NO), as its effects change dramatically depending on concentration and cellular context. Materials capable of releasing NO in deep tissues in a controlled manner might open new therapeutic opportunities. Light-sensitive NO donors represent a fascinating class of compounds with significant potential for precise and controlled NO release. However, most of them are sensitive to visible light, with only a few examples absorbing in a near-infrared therapeutic window. Here, we present the proof-of-concept of soft implants consisting of the photon upconverting core and the outer shell loaded with visible-light triggered NO donor. The separation into two compartments results in efficient energy harvesting by the dye and effective NO release under 980 nm infrared irradiation. Such implants could be used in smart therapies implying well-controlled and localized NO release.

A gated hydrophobic funnel within BAX binds long-chain alkenals to potentiate pro-apoptotic function.

Mitochondria maintain a biochemical environment that cooperates with BH3-only proteins (e.g., BIM) to potentiate BAX activation, the key event to initiate physiological and pharmacological forms of apoptosis. The sphingosine-1-phosphate metabolite 2-trans-hexadecenal (2t-hexadecenal) is one such component described to support BAX activation, but molecular mechanisms remain largely unknown. Here, we utilize complementary biochemical and biophysical techniques to reveal that 2t-hexadecenal non-covalently interacts with BAX, and cooperates with BIM to stimulate early-activation steps of monomeric BAX. Integrated structural and computational approaches reveal 2t-hexadecenal binds an undefined region - a hydrophobic cavity formed by core-facing residues of α5, α6, and gated by α8 - we now term the "BAX actuating funnel" (BAF). We define alkenal length and α8 mobility as critical determinants for 2t-hexadecenal synergy with BIM and BAX, and demonstrate that proline 168 allosterically regulates BAF function. Collectively, this work imparts detailed molecular insights advancing our fundamental knowledge of BAX regulation and identifies a regulatory region with implications for biological and therapeutic opportunities.

Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysis.

Lung adenocarcinoma (LUAD) is a major contributor to cancer-related deaths, distinguished by its pronounced tumor heterogeneity and persistent challenges in overcoming drug resistance. In this study, we utilized single-cell RNA sequencing (scRNA-seq) to dissect the roles of programmed cell death (PCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, in shaping LUAD heterogeneity, immune infiltration, and prognosis. Among these, ferroptosis and pyroptosis were most significantly associated with favorable survival outcomes, highlighting their potential roles in enhancing anti-tumor immunity. Distinct PCD-related LUAD subtypes were identified, characterized by differential pathway activation and immune cell composition. Subtypes enriched with cytotoxic lymphocytes and dendritic cells demonstrated improved survival outcomes and increased potential responsiveness to immunotherapy. Drug sensitivity analysis revealed that these subtypes exhibited heightened sensitivity to targeted therapies and immune checkpoint inhibitors, suggesting opportunities for personalized treatment strategies. Our findings emphasize the interplay between PCD pathways and the tumor microenvironment, providing insights into the mechanisms underlying tumor drug resistance and immune evasion. By linking molecular and immune features to clinical outcomes, this study highlights the potential of targeting PCD pathways to enhance therapeutic efficacy and overcome resistance in LUAD. These results contribute to a growing framework for developing precise and adaptable cancer therapies tailored to specific tumor characteristics.

Tryptophan metabolite atlas uncovers organ, age, and sex-specific variations.

Although tryptophan (Trp) is the largest and most structurally complex amino acid, it is the least abundant in the proteome. Its distinct indole ring and high carbon content enable it to generate various biologically active metabolites such as serotonin, kynurenine (Kyn), and indole-3-pyruvate (I3P). Dysregulation of Trp metabolism has been implicated in diseases ranging from depression to cancer. Investigating Trp and its metabolites in healthy tissues offers pathways to target disease-associated disruptions selectively, while preserving essential functions. In this study, we comprehensively mapped Trp metabolites across the Kyn, serotonin, and I3P pathways, as well as the microbiome-derived metabolite tryptamine, in C57BL/6 mice. Our comprehensive analysis covered 12 peripheral organs, the central nervous system, and serum in both male and female mice at three life stages: young (3 weeks), adult (54 weeks), and aged (74 weeks). We found significant tissue-, sex-, and age-specific variations in Trp metabolism, with notably higher levels of the oncometabolites I3P and Kyn in aging males. These findings emphasize the value of organ-specific analysis of Trp metabolism for understanding its role in disease progression and identifying targeted therapeutic opportunities.

Glutathione alterations in depression: a meta-analysis and systematic review of proton magnetic resonance spectroscopy studies.

Major depressive disorder (MDD) is a common and serious psychiatric disorder associated with significant morbidity. There is mounting evidence for the role of oxidative stress in the pathophysiology of depression. To investigate alterations in the brain antioxidant glutathione in depression by undertaking a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS). MEDLINE, EMBASE and Psych Info databases were searched for case-control studies that reported brain glutathione levels in patients with depression and healthy controls. Means and variances (SDS) were extracted for each measure to calculate effect sizes. Hedges g was used to quantify mean differences. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. 8 studies that reported measurements for 230 patients with depression and 216 controls were included. Three studies included data for the occipital cortex and five studies for the medial frontal cortex. In the occipital cortex, GSH was lower in the patient group as compared to controls (g = -0.98, 95% [CI, -1.45--0.50], P = < 0.001). In both the medial frontal cortex and in the combined all areas analysis there was no significant difference in GSH levels between cases and controls. This study found reduced levels of GSH specifically in the occipital region of patients with MDD. This provides some support for the role of oxidative stress in depression and suggests that targeting this system may provide future therapeutic opportunities. However, the meta-analysis was limited by the small number and quality of the included studies. More studies using high quality MRS methods in a variety of brain regions are needed in the future to test this putative hypothesis.

The Use of Personalized Medicine in Pancreatic Ductal Adenocarcinoma (PDAC): New Therapeutic Opportunities

Pancreatic cancer constitutes a significant cause of cancer-related fatalities, with a five-year survival rate of only 12%. The most prevalent form of this disease is pancreatic ductal adenocarcinoma (PDAC). Given that a single therapeutic intervention has proven inadequate for the treatment of PDAC, it is essential to identify distinct molecular signatures that could improve treatment efficacy and alleviate the economic burden on patients. Surgery is recognized as the most effective treatment option for PDAC; however, only a small percentage of patients are candidates for this procedure due to the advanced stage of the disease at the time of diagnosis. In this context, we propose to explore the biology of PDAC with a focus on microbiome, epigenetics, and genetics. Our objective is to examine the existing knowledge in these areas and to identify potential pathways for personalized medicine. This approach holds promise for advancing our understanding of PDAC development, progression, and resistance to standard therapy.

The role of ARID1A in malignant neoplasms of the female reproductive system: a modern view on diagnostic and therapeutic opportunities

Сhromatin remodeling tumor suppressor protein ARID1A (AT-rich interaction domain 1A) is coded by the ARID1A gene as one of the most frequently mutated genes in human oncological diseases. Inactivating mutations in the ARID1A gene have a pronounced effect on cell survival, chemoresistance, transcription and cell cycle regulation. To date, a large number of studies have focused on assessing the effect of mutations leading to loss of ARID1A function on tumor emergence, progression and therapy resistance. The high frequency of ARID1A mutations in malignant tumors of the female reproductive system opens up unique opportunities for targeted preventive and therapeutic intervention. Clear cell ovarian carcinoma and uterine body cancer bearing ARID1A mutations do not respond well to standard chemotherapy proposing no current effective targeted therapy, which underlines a need for further research in the field. ARID1A can be used as a biomarker of precancerous diseases, as well as as a tool for predicting а response to radiation therapy, immunotherapy and targeted therapies. Currently, clinical trials assessing several low molecular weight and epigenetic inhibitors are being conducted in tumors of the female reproductive system with ARID1A deficiency.

Exosomal signaling in cancer metastasis: Molecular insights and therapeutic opportunities.

Exosomes are membrane-bound extracellular vesicles that play a role in exchanging biological products across membranes and serve as intermediaries in intercellular communication to maintain normal homeostasis. Numerous molecules, including lipids, proteins, and nucleic acids are enclosed in exosomes. Exosomes are constantly released into the extracellular environment and exhibit distinct characteristics based on the secreted cells that produce them. Exosome-mediated cell-to-cell communication has reportedly been shown to affect multiple cancer hallmarks, such as immune response modulation, pre-metastatic niche formation, angiogenesis, stromal cell reprogramming, extracellular matrix architecture remodeling, or even drug resistance, and eventually the development and metastasis of cancer cells. Exosomes can be used as therapeutic targets and possible diagnostic biomarkers by selectively loading oncogenic molecules into them. We highlight the important roles that exosomes play in cancer development in this review, which may lead to the development of fresh approaches for future clinical uses.