New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives.

Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). Icaritin exerts its anticancer activity by modulating multiple signaling pathways, such as IL-6/JAK/STAT3, ER-α36, and NF-κB, affecting the tumor microenvironment and immune system. Several clinical trials have evaluated the safety and efficacy of icaritin in advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. The results have demonstrated that icaritin can improve survival, delay progression, and produce clinical benefits in these patients, with a favorable safety profile and minimal adverse events. Moreover, icaritin can enhance the antitumor immune response by regulating the function and phenotype of various immune cells, such as CD8+ T cells, MDSCs, neutrophils, and macrophages. These findings suggest that icaritin is a promising candidate for immunotherapy in HCC and other cancers. However, further studies are needed to elucidate the molecular mechanisms and optimal dosing regimens of icaritin and its potential synergistic effects with other agents. Therefore, this comprehensive review of the scientific literature aims to summarize advances in the knowledge of icaritin in preclinical and clinical studies as well as the pharmacokinetic, metabolism, toxicity, and mechanisms action to recognize the main challenge, gaps, and opportunities to develop a medication that cancer patients can use. Thus, our main objective was to clarify the current state of icaritin for use as an anticancer drug.

3,3'-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways.

Dietary compounds in cancer prevention have gained significant consideration as a viable method. Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are heterocyclic and bioactive chemicals found in cruciferous vegetables like broccoli, cauliflower, cabbage, and brussels sprouts. They are synthesized after glycolysis from the glucosinolate structure. Clinical and preclinical trials have evaluated the pharmacokinetic/pharmacodynamic, effectiveness, antioxidant, cancer-preventing (cervical dysplasia, prostate cancer, breast cancer), and anti-tumor activities of I3C and DIM involved with polyphenolic derivatives created in the digestion showing promising results. However, the exact mechanism by which they exert anti-cancer and apoptosis-inducing properties has yet to be entirely understood. Via this study, we update the existing knowledge of the state of anti-cancer investigation concerning I3C and DIM chemicals. We have also summarized; (i) the recent advancements in the use of I3C/DIM as therapeutic molecules since they represent potentially appealing anti-cancer agents, (ii) the available literature on the I3C and DIM characterization, and the challenges related to pharmacologic properties such as low solubility, and poor bioavailability, (iii) the synthesis and semi-synthetic derivatives, (iv) the mechanism of anti-tumor action in vitro/in vivo, (v) the action in cellular signaling pathways related to the regulation of apoptosis and anoikis as well as the cell cycle progression and cell proliferation such as peroxisome proliferator-activated receptor and PPARγ agonists; SR13668, Akt inhibitor, cyclins regulation, ER-dependent-independent pathways, and their current medical applications, to recognize research opportunities to potentially use these compounds instead chemotherapeutic synthetic drugs.

Current Status of the Therapeutic Approach for Dysmenorrhea.

Dysmenorrhea is the combination of cramps and pain associated with the menstrual period, and the symptoms affect at least 30% of women worldwide. Tolerance to symptoms depends on each person's pain threshold; however, dysmenorrhea seriously affects daily activities and chronically reduces the quality of life. Some dysmenorrhea cases even require hospitalization due to unbearable symptoms of severe pain. Dysmenorrhea is an underestimated affectation and remains even in different first-world countries as a taboo subject, promoted by the establishment of an apparent policy of gender equality. A person with primary or secondary dysmenorrhea requires medical assistance in choosing the best treatment and an integral approach. This review intends to demonstrate the impact of dysmenorrhea on quality of life. We describe the pathophysiology of this disorder from a molecular point of view and perform a comprehensive compilation and analysis of the most critical findings in the therapeutic management of dysmenorrhea. Likewise, we propose an interdisciplinary approach to the phenomenon of dysmenorrhea at the cellular level in a concise way and the botanical, pharmacological, and medical applications for its management. Since dysmenorrhea symptoms can vary between individuals, medical treatment cannot be generalized and depends on each patient. Therefore, we hypothesized that a suitable strategy could result from the combination of pharmacological therapy aided by a non-pharmacological approach.

Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest.

Cervical cancer (CC) is one of the most common cancers in women, and is linked to human papillomavirus (HPV) infection. The virus oncoprotein E6 binds to p53, resulting in its degradation and allowing uncontrolled cell proliferation. Meanwhile, the HPV E7 protein maintains host cell differentiation by targeting retinoblastoma tumor suppressor. The host cell can ubiquitinate E6 and E7 through UBE2L3, whose expression depends on the interaction between the aryl hydrocarbon receptor (AhR) with Xenobiotic Responsive Elements (XREs) located in the UBE2L3 gene promoter. In this study, we used cell culture to determine the effect of indole-3-carbinol (I3C) over cellular viability, apoptosis, cell proliferation, and mRNA levels of UBE2L3 and CYP1A1. In addition, patients' samples were used to determine the mRNA levels of UBE2L3 and CYP1A1 genes. We found that I3C promotes the activation of AhR and decreases cell proliferation, possibly through UBE2L3 mRNA induction, which would result in the ubiquitination of HPV E7. Since there is a strong requirement for selective and cost-effective cancer treatments, natural AhR ligands such as I3C could represent a novel strategy for cancer treatment.

LKB-1 Expression and High-Risk Histopathology are Independent Prognostic Factors for Patients with Oral Cavity Carcinoma.

BACKGROUND: The expression of liver kinase B1 (LKB-1) has been associated with prognosis in squamous cell carcinoma of the oral cavity (SCCOC). This study aimed to define the prognostic role of LKB-1 expression for patients with SCCOC and the suitability of its integration into a multivariate prognostic model. METHODS: A retrospective cohort study of patients with SCCOC was conducted in a cancer center. Expression of LKB-1 was evaluated by immunohistochemistry, and multivariate analysis defined prognostic factors associated with recurrence, recurrence-free survival (RFS), and overall survival (OS). The logistic regression model was used to construct a predictive computer software program. RESULTS: Of the 201 patients in this study, 104 (51.7%) experienced recurrence of their disease. Lower expression of LKB-1, high-risk histopathology, and advanced tumor-node-metastasis (TNM) stages were independent factors via multivariate analysis associated with the increased recurrence risk, poor RFS, and poor OS. If lack of LKB-1 expression is considered the reference category, the factors independently associated with recurrence were low (odds ratio [OR], 0.157; 95% confidence interval [CI], 0.044-0.557), intermediate (OR, 0.073; 95% CI, 0.017-0.319), and intense (OR, 0.047; 95% CI, 0.007-0.304) expression of LKB-1. This model permitted construction of a computer software program capable of prediction with receiver operating characteristic analysis (area under the curve, 0.925) and led to the definition of five prognostic groups with a biologic gradient. CONCLUSION: These results suggest that LKB-1 expression in patients with SCCOC is of robust prognostic value and complements the TNM staging system. The proposed model requires external validation in prospective observational studies.

The high methylation level of a novel 151-bp CpG island in the ESR1 gene promoter is associated with a poor breast cancer prognosis.

BACKGROUND: The ESR1 gene suffers methylation changes in many types of cancers, including breast cancer (BC), the most frequently diagnosed cancer in women that is also present in men. Methylation at promoter A of ESR1 is the worse prognosis in terms of overall survival; thus, the early detection, prognostic, and prediction of therapy involve some methylation biomarkers. METHODS: Therefore, our study aimed to examine the methylation levels at the ESR1 gene in samples from Mexican BC patients and its possible association with menopausal status. RESULTS: We identified a novel 151-bp CpG island in the promoter A of the ESR1 gene. Interestingly, methylation levels at this CpG island in positive ERα tumors were approximately 50% less than negative ERα or control samples. Furthermore, methylation levels at ESR1 were associated with menopausal status. In postmenopausal patients, the methylation levels were 1.5-fold higher than in premenopausal patients. Finally, according to tumor malignancy, triple-negative cancer subtypes had higher ESR1 methylation levels than luminal/HER2+ or luminal A subtypes. CONCLUSIONS: Our findings suggest that methylation at this novel CpG island might be a promising prognosis marker.

Curcumin for parkinson´s disease: potential therapeutic effects, molecular mechanisms, and nanoformulations to enhance its efficacy.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders worldwide. It is caused by the degeneration of dopaminergic neurons from the substantia nigra pars compacta. This neuronal loss causes the dopamine deficiency that leads to a series of functional changes within the basal ganglia, producing motor control abnormalities. L-DOPA is considered the gold standard for PD treatment, and it may alleviate its clinical manifestations for some time. However, its prolonged administration produces tolerance and several severe side effects, including dyskinesias and gastrointestinal disorders. Thus, there is an urgent need to find effective medications, and current trends have proposed some natural products as emerging options for this purpose. Concerning this, curcumin represents a promising bioactive compound with high therapeutic potential. Diverse studies in cellular and animal models have suggested that curcumin could be employed for the treatment of PD. Therefore, the objective of this narrative mini-review is to present an overview of the possible therapeutic effects of curcumin and the subjacent molecular mechanisms. Moreover, we describe several possible nanocarrier-based approaches to improve the bioavailability of curcumin and enhance its biological activity.

Development of films from natural sources for infections during wound healing.

The skin is the largest organ in the human body, and due to its barrier function, it is susceptible to multiple injuries. The appearance of infections during the wound healing process is a complication that represents a formidable hospital challenge. The presence of opportunistic bacteria with sophisticated resistance mechanisms is difficult to eradicate and compromises patients' lives. Therefore, the search for new efficacious treatments from natural sources that prevent and counteract infections, in addition to promoting the healing process, has increased in recent years. In this respect, films with the capability to protect wounds and release drugs are the presentation that predominates commercially in the hospital environment. Those films can offer several mechanical advantages such as physical protection to prevent opportunistic bacteria's entry, regulation of gas exchange, and capture of exudate through a swelling process. Wound dressings are generally curative materials easily adaptable to different anatomical regions, with high strength and elasticity, and some are even bioabsorbable. Additionally, the components of the films can actively participate in promoting the healing process. Even more, the film can be made up of carriers with other active participants to prevent and eradicate infections. Therefore, the extensive versatility, practicality, and usefulness of films from natural sources to address infectious processes during wound healing are relevant and recurrent themes. This work presents an analysis of the state-of-the-art of films with natural products focused on preventing and eradicating infections in wound healing.

Development of a guar gum film with lysine clonixinate for periodontal treatments.

Periodontal pain is a public health problem derived from different conditions, including periodontal diseases, prosthetic complications, and even extractions performed by dentist. There are various treatments to control acute dental pain, being the administration of analgesics, such as Lysine Clonixinate (LC), a common practice. Unfortunately, higher and repeated dosages are usually required. The purpose of this work was to develop a prolonged release pharmaceutical form as an alternative treatment for dental pain. Hence, we conceived a film based on guar gum and loaded different concentrations of LC. We evaluated the film's appearance, brittleness, strength, and flexibility, and then chose one formulation for adequate characteristics. Subsequently, we assessed the morphology, thermal behavior, and swelling properties of the films (LC-free and -loaded). Finally, we performed the release studies of LC from the films in vitro using a simulated saliva medium and employed several mathematical models to evaluate the release kinetics. Guar gum is a natural polymer obtained from the endosperm of Cyamopsis tetragonolobus that presents properties such as biosafety, biocompatibility, and biodegradability. Thus, it represents a potential excipient for use in pharmaceutical formulations. Moreover, our results revealed that the LC-loaded film presented a high adherence, suitable swelling behavior, high LC content, and a prolonged drug release. Therefore, the LC-loaded film may be considered a potential option to be applied as an alternative to treat dental pain.

Development of a xanthan gum film for the possible treatment of vaginal infections.

Bacterial vaginosis is a vaginal infection that affects 60% of women of reproductive age worldwide. It is mainly caused by the bacterium Gardnerella vaginalis and is a factor that increases the probability of getting sexually transmitted diseases. We aimed to develop a new pharmaceutical form for the treatment of vaginal infections. We employed the solving-casting method to fabricate a polymeric film with Xanthan gum, a natural polymer produced by the bacterium Xanthomonas campestris, and metronidazole, one of the most commonly used drugs for vaginal infections. In order to characterize the film, we measured pH, dose uniformity, dissolution profile, and the percentage of swelling. Moreover, we performed a thermogravimetric analysis and scanning electron microscopy. The results demonstrated a pH suitable for vaginal application and uniform distribution of the drug in the film. Also, the formulation exhibited a high percentage of swelling and a slow release of the drug in a simulated vaginal fluid medium. All these attributes indicated that the manufactured film has ideal characteristics to be used and administered vaginally. It could be an excellent alternative to treat bacterial vaginosis and also improve user adherence.

Physicochemical and biological characterization of a xanthan gum-polyvinylpyrrolidone hydrogel obtained by gamma irradiation.

Xanthan gum (XG) and polyvinylpyrrolidone (PVP) are two polymers with low toxicity, high biocompatibility, biodegradability, and high hydrophilicity, making them promising candidates for multiple medical aspects. The present work aimed to synthesize a hydrogel from a mixture of XG and PVP and crosslinked by gamma irradiation. We assessed the hydrogel through a series of physicochemical (FT-IR, TGA, SEM, and percentage of swelling) and biological (stability of the hydrogel in cell culture medium) methods that allowed to determine its applicability. The structural evaluation by infrared spectrum demonstrated that a crosslinked hydrogel was obtained from the combination of polymers. The calorimetric test and swelling percentage confirmed the formation of the bonds responsible for the crosslinked structure. The calorimetric test evidenced that the hydrogel was resistant to decomposition in contrast to non- irradiated material. The determination of the swelling degree showed constant behavior over time, indicating a structure resistant to hydrolysis. This phenomenon also occurred during the test of stability in a cell culture medium. Additionally, microscopic analysis of the sample revealed an amorphous matrix with the presence of porosity. Thus, the findings reveal the synthesis of a novel material that has desirable attributes for its potential application in pharmaceutical and biomedical areas.

Radiation-induced graft polymerization of elastin onto polyvinylpyrrolidone as a possible wound dressing.

The purpose of our study was to obtain new wound dressings in the form of hydrogels that promote wound healing taking advantage of the broad activities of elastin (ELT) in physiological processes. The hydrogel of ELT and polyvinylpyrrolidone (PVP; ELT-PVP) was obtained by cross-linking induced by gamma irradiation at a dose of 25 kGy. The physicochemical changes attributed to cross-linking were analyzed through scanning electron microscopy (SEM), infrared spectroscopy analysis with Fourier transform (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Furthermore, we performed a rheological study to determine the possible changes in the fluidic macroscopic properties produced by the cross-linking method. Finally, we accomplished viability and proliferation analyses of human dermal fibroblasts in the presence of the hydrogel to evaluate its biological characteristics. The hydrogel exhibited a porous morphology, showing interconnected porous with an average pore size of 16 ± 8.42 µm. The analysis of FTIR, DSC, and TGA revealed changes in the chemical structure of the ELT-PVP hydrogel after the irradiation process. Also, the hydrogel exhibited a rheological behavior of a pseudoplastic and thixotropic fluid. The hydrogel was biocompatible, demonstrating high cell viability, whereas ELT presented low biocompatibility at high concentrations. In summary, the hydrogel obtained by gamma irradiation revealed the appropriate morphology to be applied as a wound dressing. Interestingly, the hydrogel exhibited a higher percentage of cell viability compared with ELT, suggesting that the cross-linking of ELT with PVP is a suitable strategy for biological applications of ELT without generating cellular damage.

Synthesis by gamma irradiation of hyaluronic acid-polyvinyl alcohol hydrogel for biomedical applications.

Hyaluronic acid (HA) is one of the most attractive natural polymers employed in biomaterials with biological applications. This polysaccharide is found in different tissues of the body because it is a natural component of the extracellular matrix; furthermore, it has crucial functions in cell growth, migration, and differentiation. Since its biological characteristics, HA has been utilized for the new biomaterial's development for tissue engineering, such as hydrogels. These hydrophilic macromolecular networks have gained significant attention due to their unique properties, making them potential candidates to be applied in biomedical fields. Different mechanisms to obtain hydrogels have been described. However, the research of new non-toxic methods has been growing in recent years. In this study, we prepared a new hydrogel of HA and polyvinyl alcohol by the cost-effective technique of cross-linking by gamma irradiation. The hydrogel was elaborated for the first time and was characterized by several methods such as Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry, Thermogravimetric Analysis, and Scanning Electron Microscopy. Likewise, we evaluated the cytotoxicity of the biomaterial and its influence on cell migration in human fibroblasts. Furthermore, we provide preliminary evidence of the wound closure effect in a cellular wound model. The novel hydrogel offers an increase of HA stability with the potential to expand the useful life of HA in its different medical applications.

Insights into Terminal Sterilization Processes of Nanoparticles for Biomedical Applications.

Nanoparticles possess a huge potential to be employed in numerous biomedical purposes; their applications may include drug delivery systems, gene therapy, and tissue engineering. However, the in vivo use in biomedical applications requires that nanoparticles exhibit sterility. Thus, diverse sterilization techniques have been developed to remove or destroy microbial contamination. The main sterilization methods include sterile filtration, autoclaving, ionizing radiation, and nonionizing radiation. Nonetheless, the sterilization processes can alter the stability, zeta potential, average particle size, and polydispersity index of diverse types of nanoparticles, depending on their composition. Thus, these methods may produce unwanted effects on the nanoparticles' characteristics, affecting their safety and efficacy. Moreover, each sterilization method possesses advantages and drawbacks; thus, the suitable method's choice depends on diverse factors such as the formulation's characteristics, batch volume, available methods, and desired application. In this article, we describe the current sterilization methods of nanoparticles. Moreover, we discuss the advantages and drawbacks of these methods, pointing out the changes in nanoparticles' biological and physicochemical characteristics after sterilization. Our main objective was to offer a comprehensive overview of terminal sterilization processes of nanoparticles for biomedical applications.

Hyaluronic acid in wound dressings.

Human skin possesses an essential function in the maintenance of individuals' health. However, it may undergo a variety of lesions that produce wounds of distinct severity. In this respect, instantly after any skin wound, the process of tissue regeneration and repair initiates. Nevertheless, diverse factors can delay this process, including bacterial infections, nutritional status, age, hypoxia, chronic diseases, necrosis, and vascular and arterial diseases. Thus, wound dressings are frequently used to improve wound healing. Those wound dressings are fabricated with diverse materials, which confer them different properties. In this regard, hyaluronic acid is a natural polysaccharide widely distributed in extracellular matrices of mammal tissues, which possesses remarkable attributes in terms of biocompatibility, biodegradability, and low cost. Moreover, hyaluronic acid exhibits several beneficial effects on wound healing, such as the decrease of inflammatory processes, regulation of tissue remodeling, and enhancement of angiogenesis. Therefore, in recent years, there is growing attention in this polysaccharide for the design and manufacture of novel wound dressings, which have shown encouraging properties. Here, we describe the different approaches of hyaluronic acid for the production of wound dressings, encompassing hydrogels, films, scaffolds, foams, topical formulations, and nanoformulations, as well as its beneficial effects on wound healing. Finally, we discuss perspectives about the use of hyaluronic acid in wound dressings.

Xanthan gum in drug release.

Controlled release is of vital relevance for many drugs; thus, there is a keen interest in materials that can improve the release profiles of formulations administered via buccal, transdermal, ophthalmic, vaginal, and nasal. The desirable effects of those materials include the improvement of stability, adhesiveness, solubility, and retention time. Hence, different synthetic and natural polymers are utilized to achieve these objectives. In this respect, xanthan gum is an anionic polysaccharide that can be obtained from Xanthomonas bacteria. It is a natural polymer broadly employed in numerous food products, lotions, shampoos, and dermatological articles. Furthermore, due to its physicochemical features, xanthan gum is growingly utilized for the development and improvement of drug delivery systems. In this regard, encouraging findings have been revealed by recent formulations for pharmaceutical applications, including antiviral carriers, antibacterial transporters, transdermal patches, vaginal formulations, and anticancer medications. In this article, we perform a concise description of the chemical properties of xanthan gum and its role as a modifier of drug release. Furthermore, we present an outlook of the state of the art of research focused on the utilization of xanthan gum in varied pharmaceutical formulations, which include tablets, films, hydrogels, and nanoformulations. Finally, we discuss some perspectives about the use of xanthan gum in these formulations.

Cell migration and proliferation are regulated by miR-26a in colorectal cancer via the PTEN-AKT axis.

BACKGROUND: Invasion and metastasis are determinant events in the prognosis of Colorectal cancer (CRC), a common neoplasm worldwide. An important factor for metastasis is the acquired capacity of the cell to proliferate and invade adjacent tissues. In this paper, we explored the role of micro-RNA-26a in the regulation of proliferation and migration in CRC-derived cells through the negative regulation of PTEN, a key negative regulator of the AKT pathway. METHODS: Expression levels of PTEN and mir-26a were surveyed in normal and CRC-derived cell lines; paraffin embedded human tissues, TCGA CRC expression data and a Balb/c mice orthotopic induced CRC model. CRC was induced by an initial intraperitoneal dose of the colonic carcinogen Azoxymethane followed by inflammatory promoter Dextran Sulfate Sodium Salt. Luciferase assays provide information about miR-26a-PTEN 3'UTR interaction. Proliferation and migration by real time cell analysis and wound-healing functional analyses were performed to assess the participation of mir-26a on important hallmarks of CRC and its regulation on the PTEN gene. RESULTS: We observed a negative correlation between PTEN and mir-26a expression in cell lines, human tissues, TCGA data, and tissues derived from the CRC mouse model. Moreover, we showed that negative regulation of PTEN exerted by miR-26a affected AKT phosphorylation levels directly. Functional assays showed that mir-26a directly down-regulates PTEN, and that mir-26a over-expressing cells had higher proliferation and migration rates. CONCLUSIONS: All this data proposes an important role of mir-26a as an oncomir in the progression and invasion of CRC. Our data suggested that mir-26a could be used as a biomarker of tumor development in CRC patients, however more studies must be conducted to establish its clinical role.

Long Non-Coding RNAs as New Master Regulators of Resistance to Systemic Treatments in Breast Cancer.

Predicting response to systemic treatments in breast cancer (BC) patients is an urgent, yet still unattained health aim. Easily detectable molecules such as long non-coding RNAs (lncRNAs) are the ideal biomarkers when they act as master regulators of many resistance mechanisms, or of mechanisms that are common to more than one treatment. These kinds of markers are pivotal in quasi-personalized treatment selection, and consequently, in improvement of outcome prediction. In order to provide a better approach to understanding development of disease and resistance to treatments, we reviewed current literature searching for lncRNA-associated systemic BC treatments including endocrine therapies, aromatase inhibitors, selective estrogen receptor modulators (SERMs), trastuzumab, paclitaxel, docetaxel, 5-fluorouracil (5-FU), anthracyclines, and cisplatin. We found that the engagement of lncRNAs in resistance is well described, and that lncRNAs such as urotelial carcinoma-associated 1 (UCA1) and regulator of reprogramming (ROR) are indeed involved in multiple resistance mechanisms, which offers tantalizing perspectives for wide usage of lncRNAs as treatment resistance biomarkers. Thus, we propose this work as the foundation for a wide landscape of functions and mechanisms that link more lncRNAs to resistance to current and new treatments in years of research to come.

Comprehensive transcriptome analysis identifies pathways with therapeutic potential in locally advanced cervical cancer.

OBJECTIVE: The objective of the present study was to provide genomic and transcriptomic information that may improve clinical outcomes for locally advanced cervical cancer (LACC) patients by searching for therapeutic targets or potential biomarkers through the analysis of significantly altered signaling pathways in LACC. METHODS: Microarray-based transcriptome profiling of 89 tumor samples from women with LACC was performed. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, significantly over-expressed genes in LACC were identified; these genes were validated by quantitative reverse transcription-polymerase chain reaction in an independent cohort, and the protein expression data were obtained from the Human Protein Atlas. RESULTS: A transcriptome analysis revealed 7530 significantly over-expressed genes in LACC samples. By KEGG analysis, we found 93 dysregulated signaling pathways, including the JAK-STAT, NOTCH and mTOR-autophagy pathways, which were significantly upregulated. We confirmed the overexpression of the relevant genes of each pathway, such as NOTCH1, JAK2, STAM1, SOS1, ADAM17, PSEN1, NCSTN, RPS6, STK11/LKB1 and MLTS8/GBL in LACC compared with normal cervical tissue epithelia. CONCLUSIONS: Through comprehensive genomic and transcriptomic analyses, this work provides information regarding signaling pathways with promising therapeutic targets, suggesting novel target therapies to be considered in future clinical trials for LACC patients.