Microbiomes, epigenomics, immune response, and splicing signatures interplay : potential use of combination of regulatory pathways as targets for malignant mesothelioma

Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome–epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed.The Department of Surgery, University of Pretoria, the South African Medical Research Council (SAMRC) and the National Research Foundation (NRF).https://www.mdpi.com/journal/ijerphMedical OncologySurger

MicroRNA interrelated epithelial mesenchymal transition (EMT) in glioblastoma

MicroRNAs (miRNA) are small non-coding RNAs that are 20–23 nucleotides in length, functioning as regulators of oncogenes or tumor suppressor genes. They are molecular modulators that regulate gene expression by suppressing gene translation through gene silencing/degradation, or by promoting translation of messenger RNA (mRNA) into proteins. Circulating miRNAs have attracted attention as possible prognostic markers of cancer, which could aid in the early detection of the disease. Epithelial to mesenchymal transition (EMT) has been implicated in tumorigenic processes, primarily by promoting tumor invasiveness and metastatic activity; this is a process that could be manipulated to halt or prevent brain metastasis. Studies show that miRNAs influence the function of EMT in glioblastomas. Thus, miRNA-related EMT can be exploited as a potential therapeutic target in glioblastomas. This review points out the interrelation between miRNA and EMT signatures, and how they can be used as reliable molecular signatures for diagnostic purposes or targeted therapy in glioblastomas.South African Medical Research Council (SAMRC) and National Research Foundation (NRF).https://www.mdpi.com/journal/genesam2023ImmunologyMedical OncologyOral Pathology and Oral BiologySurger

AI and precision oncology in clinical cancer genomics : from prevention to targeted cancer therapies-an outcomes based patient care

Precision medicine is the personalization of medicine to suit a specific group of people or even an individual patient, based on genetic or molecular profiling. This can be done using genomic, transcriptomic, epigenomic or proteomic information. Personalized medicine holds great promise, especially in cancer therapy and control, where precision oncology would allow medical practitioners to use this information to optimize the treatment of a patient. Personalized oncology for groups of individuals would also allow for the use of population group specific diagnostic or prognostic biomarkers. Additionally, this information can be used to track the progress of the disease or monitor the response of the patient to treatment. This can be used to establish the molecular basis for drug resistance and allow the targeting of the genes or pathways responsible for drug resistance. Personalized medicine requires the use of large data sets, which must be processed and analysed in order to identify the particular molecular patterns that can inform the decisions required for personalized care. However, the analysis of these large data sets is difficult and time consuming. This is further compounded by the increasing size of these datasets due to technologies such as next generation sequencing (NGS). These difficulties can be met through the use of artificial intelligence (AI) and machine learning (ML). These computational tools use specific neural networks, learning methods, decision making tools and algorithms to construct and improve on models for the analysis of different types of large data sets. These tools can also be used to answer specific questions. Artificial intelligence can also be used to predict the effects of genetic changes on protein structure and therefore function. This review will discuss the current state of the application of AI to omics data, specifically genomic data, and how this is applied to the development of personalized or precision medicine on the treatment of cancer.The South African Medical Research Council (SAMRC) and the National Research Foundation (NRF).https://www.elsevier.com/locate/imuhj2023Anatomical PathologyMaxillo-Facial and Oral SurgeryMedical OncologyOtorhinolaryngologyRadiologySurgeryUrolog

Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma

Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome–epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed

Prostate cancer racial, socioeconomic, geographic disparities : targeting the genomic landscape and splicing events in search for diagnostic, prognostic and therapeutic targets

Prostate cancer (PCa) is one of the leading causes of deaths in men globally. This is a heterogeneous and complex disease that urgently warrants further insight into its pathology. Developed countries have thus far the highest PCa incidence rates, with comparatively low mortality rates. Even though PCa in the Asian population seems to have high incidence and mortality rates, the African countries are emerging as the focal center for this disease. It has also been reported that the Sub-Saharan (SSA) countries have both the highest incidence and mortality rates. To date, few studies have reported the link between PCa and African populations. Adequate evidence is still missing to fully comprehend this relationship. While it has been brought to attention that racial, geographical and socioeconomic status are contributing factors, men of African descent across the globe, irrespective of their geographical position have higher PCa incidence and mortality rates compared to their white counterparts. To date, hormone therapy is the mainstay treatment of PCa, while the dysregulation of androgen receptor (AR) signaling is a hallmark of PCa. One of the emerging problems with this therapeutic approach is resistance to antiandrogens, and that AR splice isoforms implicated in the progression of PCa lack the therapeutic ligand-binding domain (LBD) target. AR splice variants targeted therapy is emerging and in clinical trials. Leveraging PCa transcriptomics is key towards PCa precision medicine. The aim of this review is to outline the PCa epidemiology globally and in Africa, PCa associated risk factors, discuss AR signaling and PCa mechanisms, the role of dysregulated splicing in PCa as novel prognostic indicators and therapeutic targets.South African Medical Research Council (SAMRC)http://www.ajcr.uspm2021SurgeryUrolog

Immunosuppressive signaling pathways as targeted cancer therapies

Immune response has been shown to play an important role in defining patient prognosis and response to cancer treatment. Tumor-induced immunosuppression encouraged the recent development of new chemotherapeutic agents that assists in the augmentation of immune responses. Molecular mechanisms that tumors use to evade immunosurveillance are attributed to their ability to alter antigen processing/presentation pathways and the tumor microenvironment. Cancer cells take advantage of normal molecular and immunoregulatory machinery to survive and thrive. Cancer cells constantly adjust their genetic makeup using several mechanisms such as nucleotide excision repair as well as microsatellite and chromosomal instability, thus giving rise to new variants with reduced immunogenicity and the ability to continue to grow without restrictions. This review will focus on the central molecular signaling pathways involved in immunosuppressive cells and briefly discuss how cancer cells evade immunosurveillance by manipulating antigen processing cells and related proteins. Secondly, the review will discuss how these pathways can be utilized for the implementation of precision medicine and deciphering drug resistanceSouth African Medical Research Council (SAMRC) and National Research Foundation (NRF).http://www.mdpi.com/journal/biomedicinesSurger