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Abstract The p53 mutation is the most common genetic mutation associated with human neoplasia. TP53 missense mutations, which frequently arise early in breast cancer, are present in over thirty percent of breast tumors. In breast cancer, p53 mutations are linked to a more aggressive course of the disease and worse overall survival rates. TP53 mutations are mostly seen in triple-negative breast cancer, a very diverse kind of the disease. The majority of TP53 mutations originate in the replacement of individual amino acids within the p53 protein's core domain, giving rise to a variety of variations referred to as "mutant p53s." In addition to gaining carcinogenic qualities through gain-of-function pathways, these mutants lose the typical tumor-suppressive features of p53 to variable degrees. The gain-of-function impact of stabilized mutant p53 causes tumor-specific dependency and resistance to therapy. P53 is a prospective target for cancer therapy because of its tumor-suppressive qualities and the numerous alterations that it experiences in tumors. Phenotypic abnormalities in breast cancer, notably poorly differentiated basal-like tumors are frequently linked to high-grade tumors. By comparing data from cell and animal models with clinical outcomes in breast cancer, this study investigates the molecular mechanisms that convert gene alterations into the pathogenic consequences of mutant p53's tumorigenic activity. The study delves into current and novel treatment approaches aimed at targeting p53 mutations, taking into account the similarities and differences in p53 regulatory mechanisms between mutant and wild-type forms, as well. Graphical Abstract

It is predicted that over 29 million individuals will receive a cancer diagnosis in 2040, making cancer one of the major causes of death globally. One of the biggest obstacles to being overcome in the treatment of cancer is drug resistance, which is mostly to blame for this high death rate. Research has therefore concentrated on developing new therapeutic tools, particularly those that enable individualized care based on the features of the patient. Although ensuring the quality of life for cancer patients has been a concern for the scientific community, attempts have been made to find alternatives to the creation of new pharmaceuticals since researchers are aware of the rising expenses associated with cancer therapy. The trend towards drug repurposing is growing as a strategy to accelerate drug development, utilizing the proven safety and effectiveness of existing approved drugs. The central theme of this review centered on exploring potential repurposed medications for treating cancer. The central theme of this review revolves around Adapalene, traditionally known for its acne treatment benefits, now being evaluated for its potential in cancer therapy. The latest details of Adapalene, a repurposed cancer therapeutic candidate, its therapeutic potential, Pharmacokinetic Profile, and the molecular interactions behind its anti-tumor efficacy are also included in this paper. In addition, medication combinations have also been covered here as a useful tactic to get around the restrictions associated with drug repurposing. The review concludes that drug repurposing represents one of the most promising approaches in cancer treatment and incorporating combination therapy can address challenges encountered in this field. Regarding drug repurposing, Adapalene has demonstrated significant efficacy in treating various types of cancer, including skin cancer, colon cancer, and breast cancer.

IntroductionThe members retinoic acid receptors (RARs) (α, β, and γ) and retinoid X receptors (RXRs) (α, β, and γ) belong to the retinoid receptor family. They regulate the biological action of classical retinoids through nuclear retinoid receptors, a transcription factor that is regulated by ligands. Through the binding of particular retinoic acid-responsive elements (RAREs) located in target gene promoters, RARs and members of the RXRs form heterodimers. By binding to its nuclear receptors and triggering the transcription of the target genes downstream, retinoic acid (RA) mediates the expression of certain genes. Retinoids so mainly control gene expression to carry out their biological actions. RARs are essential for many biological processes, such as development, immunity, reproduction, organogenesis, and homeostasis. Apart from their physiological functions, RARs are also linked to pathologies and tumors due to mutations, protein fusions, changes in expression levels, or abnormal post-translational changes that lead to aberrant functions and homeostasis breakdown. The oncogenic development of animal tissues or cultured cells is linked to altered expression of retinoid receptors. The RAR-α is over-expressed in several malignancies. Increased invasion and migration in several cancer forms, including HNSC carcinoma, pediatric low-grade gliomas, lung adenocarcinoma, and breast cancer, have been linked to its upregulated expression. Numerous approved therapeutic regimens targeting RAR-α have been developed, improving patient survival rates.ObjectiveThis study’s main objective was to identify novel RAR-α-targeting drugs and evaluate the expression patterns of RAR-α in breast cancer patients.MethodologyIn-silico investigation using a variety of bioinformatics tools like UALCAN, TISCH, TIMER 2.0, ENRICHR, and others were employed to examine the expression of RAR-α. Further we evaluated in-silico inhibition of RAR-α with trifarotene and also tested the cytotoxicity of trifarotene in breast cancer cells.ResultsOur research indicates that RAR-α is upregulated in several malignancies including Breast Cancer. It regulates granulocyte differentiation and has an association with the retinoic acid receptor signaling pathway and cellular response to estrogen stimulus. Furthermore, trifarotene was found as a potential synthetic compound that targets RAR-α through in silico and in-vitro study.DiscussionOverall, this research indicates that elevated expression of RAR-α enhances the onset of breast cancer. Using trifarotene medication to target RAR-α will significantly boost the response of breast cancer individuals to treatment and delay the development of resistance to drugs.

Cancer represents a significant global health and economic burden due to its high mortality rates. While effective in some instances, traditional chemotherapy often falls short of entirely eradicating various types of cancer. It can cause severe side effects due to harm to healthy cells. Two therapeutic approaches have risen to the forefront to address these limitations: metronomic chemotherapy (MCT) and drug repurposing. Metronomic chemotherapy is an innovative approach that breaks from traditional models. It involves the administration of chemotherapeutic regimens at lower doses, without long drug-free intervals that have previously been a hallmark of such treatments. This method offers a significant reduction in side effects and improved disease management. Simultaneously, drug repurposing has gained considerable attraction in cancer treatment. This approach involves utilizing existing drugs, initially developed for other therapeutic purposes, as potential cancer treatments. The application of known drugs in a new context accelerates the timeline from laboratory to patient due to pre-existing safety and dosage data. The intersection of these two strategies gives rise to a novel therapeutic approach named ‘Metronomics.’ This approach encapsulates the benefits of both MCT and drug repurposing, leading to reduced toxicity, potential for oral administration, improved patient quality of life, accelerated clinical implementation, and enhanced affordability. Numerous clinical studies have endorsed the efficacy of metronomic chemotherapy with tolerable side effects, underlining the potential of Metronomics in better cancer management, particularly in low- and middle-income countries. This review underscores the benefits and applications of metronomic chemotherapy and drug repurposing, specifically in the context of breast cancer, showcasing the promising results of pre-clinical and clinical studies. However, we acknowledge the necessity of additional clinical investigations to definitively establish the role of metronomic chemotherapy in conjunction with other treatments in comprehensive cancer management.

Cancer continues to be a major global public health concern and one of the foremost causes of death. Delays in the diagnosis and cure may cause an increase in advanced stage disease and mortality. The most common cancer found in women currently is breast carcinoma. Breast carcinoma has surpassed lung carcinoma and currently represents the chief type of cancer diagnosed (2.3 million new cases, which amount to 11.7% of all cancer cases). In addition, by 2040, the incidence will increase by more than 46% as per the estimates of GLOBOCAN. Triple-negative breast cancer (TNBC) represents a highly aggressive and invasive subtype of breast cancer, characterized by rapid progression, short response time to the available treatment, and poor clinical results. Thus, it is very crucial to develop novel diagnostic tools and therapeutics with good efficacy. A majority of cancers display malfunction along the p53 pathway. Moreover, p53 not only loses its function but is also prone to misfolding and aggregation, leading to formation of amyloid aggregates as well. Research is being carried out to find ways to restore the normal action and expression of p53. Here, we have explored PhiKan-083 for its possible stabilizing effect on p53 in order to address the problem with its misfolding. Thus, examining the analogs of PhiKan-083 that have a role in p53 stability will help update our understanding of cancer progression and may expedite the progress of new anticancer treatments. We anticipate that the drug molecules and their analogs targeting p53 aggregation may be used in combination with other anticancer compounds to solve the problem with p53 aggregation. In this study, by employing ADMET analysis, the compounds were screened, and we further examined the chosen compounds with the help of molecular docking. By using databases like UALCAN, TIMER, GEPIA, and PredictProtein, we investigated TP53’s expression pattern and prognostic relevance in various cancer settings.

The most recurrent type of cancer among women is breast cancer which is an intricate disease with high intertumoral and intratumoral heterogeneity. Such variability is a key factor in the failure of current treatments and the emergence of resistance. It is crucial to develop novel therapeutic options to enhance the prognosis for breast cancer patients due to the limitations of current therapy and the unavoidable formation of acquired drug resistance (chemo and endocrine) as well as radio resistance. Poor clinical results in the treatment of breast cancer, that is resistance are associated with deregulated Notch signalling within the breast tumor and its tumor microenvironment (TME). In this research, a bioinformatics approach was used to check the expression pattern, the role, as well as the prognostic and diagnostic significance of the deregulated Notch-related genes in BC patients. The various bioinformatic tools include; UCSC XENA, GEPIA 2, UALCAN, bc Genexminer, KM Plotter, ENRICHR, STRING and Cytoscape. The study demonstrates that highly dysregulated genes (NOTCH4, CCND1, JAG1, DLL1, MAML2, and EGFR) can be used as biomarkers to identify breast cancer patients with poor prognosis and as potential targets for therapeutic intervention. The study found that 6 genes—NOTCH4, CCND1, JAG1, DLL1, MAML2, and EGFR—out of 22 tested genes showed a significant log2 fold change. Our study revealed that Luminal Breast Cancer patients display a high expression of the CCND1 gene in comparison to its expression in normal. The results of our study also depicted that the patients with elevated levels of NOTCH-related gene expression displayed better relapse-free survival with p

Background: Baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, member of the inhibitor of apoptosis (IAP), is a multitasking protein and among the top 100 deregulated genes in breast cancer patients. It negatively regulates apoptosis of tumor cells by inducing gene expression of anti-apoptotic proteins, promoting tumor cell proliferation, and modulates response to chemotherapeutics. Objective: The main objective of the study was to analyze the expression pattern, prognostic significance and functional role of BIRC5 in breast cancer (BC). Methods: In the present study, we utilized a bioinformatic approach, to analyze the expression pattern and prognostic significance of BIRC5 in BC and explore the interactions of BIRC5 in promoting breast tumorigenicity. Results: BIRC5 mRNA levels were augmented in breast carcinoma & over-expression of BIRC5 was found associated with poor overall survival (OS) and relapse-free survival (RFS). The KEGG pathway and gene ontology analysis of BIRC5 indicate that BIRC5 is highly enriched in mitotic pathways and cancer pathways. The PPI and correlation analysis further revealed that BIRC5 showed high with oncogenic proteins. Moreover, BIRC5 showed high correlation with infiltration of myeloid derived suppressor cells (MDSCs) in the breast tumor stroma. Conclusions: Cumulatively, this study signifies that BIRC5 promotes tumor progression, & targeting BIRC5 in combination with conventional therapies will significantly enhance the response of BC patients to therapy.

Around the world, polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic condition that typically affects 6–20% of females. Our study’s major goal was to examine how chlorogenic acid (CGA) affected mice with endocrine and metabolic problems brought on by letrozole-induced PCOS. Group I served as the control for 81 days; Group II was given Letrozole (LETZ) orally at a dose of 6 mg/kg bw for 21 days to induce PCOS; Group III was given LETZ (6 mg/kg) for 21 days, followed by treatment with CGA (50 mg/kg bw daily) for 60 days. The study indicated that LETZ-treated mice displayed symptoms of PCOS, such as dyslipidemia, hyperinsulinemia, elevated testosterone, increases in inflammatory markers and malonaldehyde, and a decline in antioxidants (Ar, lhr, fshr, and esr2) in the ovaries. These alterations were affected when the mice were given CGA and were associated with reduced levels of adiponectin. Adiponectin showed interactions with hub genes, namely MLX interacting protein like (MLXIPL), peroxisome proliferator-activated receptor gamma Coactivator 1- alpha (PPARGC1), peroxisome proliferator-activated receptor gamma (Pparg), and adiponectin receptor 1 (Adipor1). Lastly, the gene ontology of adiponectin revealed that adiponectin was highly involved in biological processes. The findings from our research suggest that adiponectin has direct impacts on metabolic and endocrine facets of PCOS.