Role of precision oncology in type II endometrial and prostate cancers in the African population : global cancer genomics disparities

Precision oncology can be defined as molecular profiling of tumors to identify targetable alterations. Emerging research reports the high mortality rates associated with type II endometrial cancer in black women and with prostate cancer in men of African ancestry. The lack of adequate genetic reference information from the African genome is one of the major obstacles in exploring the benefits of precision oncology in the African context. Whilst external factors such as the geography, environment, health-care access and socio-economic status may contribute greatly towards the disparities observed in type II endometrial and prostate cancers in black populations compared to Caucasians, the contribution of African ancestry to the contribution of genetics to the etiology of these cancers cannot be ignored. Non-coding RNAs (ncRNAs) continue to emerge as important regulators of gene expression and the key molecular pathways involved in tumorigenesis. Particular attention is focused on activated/repressed genes and associated pathways, while the redundant pathways (pathways that have the same outcome or activate the same downstream effectors) are often ignored. However, comprehensive evidence to understand the relationship between type II endometrial cancer, prostate cancer and African ancestry remains poorly understood. The sub-Saharan African (SSA) region has both the highest incidence and mortality of both type II endometrial and prostate cancers. Understanding how the entire transcriptomic landscape of these two reproductive cancers is regulated by ncRNAs in an African cohort may help elucidate the relationship between race and pathological disparities of these two diseases. This review focuses on global disparities in medicine, PCa and ECa. The role of precision oncology in PCa and ECa in the African population will also be discussed.This research was funded by the South African Medical Research Council (SAMRC) Grant No. 23108 and the National Research Foundation (NRF) Grant No. 138139.The South African Medical Research Council and the National Research Foundation.https://www.mdpi.com/journal/ijerphMedical OncologyUrolog

mCRPC patients receiving 225Ac-PSMA-617 therapy in the post-androgen deprivation therapy setting : response to treatment and survival analysis

Please read abstract in the article.http://jnm.snmjournals.orghj2023Nuclear Medicin

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

The South African guidelines on enuresis-2017

Introduction: Enuresis (or Nocturnal Enuresis) is defined as discreet episodes of urinary incontinence during sleep in children over 5 years of age in the absence of congenital or acquired neurological disorders. Recommendations: Suggestions and recommendations are made on the various therapeutic options available within a South African context. These therapeutic options include; behavioural modification, pharmaceutical therapy [Desmospressin (DDAVP), Anticholinergic (ACh) Agents, Mirabegron (beta 3-adrenoreceptor agonists), and Tricyclic Antidepressants (TCA)], alternative treatments, complementary therapies, urotherapy, alarm therapy, psychological therapy and biofeedback. The role of the Bladder Diary, additional investigations and Mobile Phone Applications (Apps) in enuresis is also explored. Standardised definitions are also outlined within this document. Conclusion: An independent, unbiased, national evaluation and treatment guideline based on the pathophysiological subcategory is proposed using an updated, evidence based approach. This Guideline has received endorsement from the South African Urological Association, Enuresis Academy of South Africa and further input from international experts within the field

A qualitative exploration of South African men’s perceived effects of androgen deprivation therapy (ADT) as a treatment for advanced prostate cancer t

OBJECTIVE : We undertake qualitative research with men treated in a Pretoria, South Africa Oncology clinic to address men’s self-reported experiences on androgen deprivation therapy (ADT). METHODS : Analyses rely upon 22 men’s responses to open-ended questions during interviews. These men were 63–78 years of age, and almost all married (three widowed), had children and were no longer engaged in paid work. RESULTS : In addressing questions about the anticipated and experienced positive and broader side effects of ADT, men referred to its treatment for prostate cancer, with several generally specifying health or life. Patients also referred to a variety of more specific effects such as pain, nausea, difficulties urinating, gaining weight, low energy and sleep disruptions that appeared to reflect a mixture of influences of prostate cancer, ADT and oncological treatment. In addressing a question about the effects of ADT on romantic/sex life, 16 of 19 married men referred to deleterious impacts on their sex lives. With respect to perceived family, work or broader social life impacts, some men noted others’ worries and social support. CONCLUSION : Findings are situated within discussions of existing research on ADT largely from North American or European samples, and broader views of testosterone and male social behavior.https://www.tandfonline.com/toc/itam202021-05-12hj2020Urolog

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

Many voices in a choir: tumor-induced neurogenesis and neuronal driven alternative splicing sound like suspects in tumor growth and dissemination

During development, as tissues expand and grow, they require circulatory, lymphatic, and nervous system expansion for proper function and support. Similarly, as tumors arise and develop, they also require the expansion of these systems to support them. While the contribution of blood and lymphatic systems to the development and progression of cancer is well known and is targeted with anticancer drugs, the contribution of the nervous system is less well studied and understood. Recent studies have shown that the interaction between neurons and a tumor are bilateral and promote metastasis on one hand, and the formation of new nerve structures (neoneurogenesis) on the other. Substances such as neurotransmitters and neurotrophins being the main actors in such interplay, it seems reasonable to expect that alternative splicing and the different populations of protein isoforms can affect tumor-derived neurogenesis. Here, we report the different, documented ways in which neurons contribute to the development and progression of cancer and investigate what is currently known regarding cancer-neuronal interaction in several specific cancer types. Furthermore, we discuss the incidence of alternative splicing that have been identified as playing a role in tumor-induced neoneurogenesis, cancer development and progression. Several examples of changes in alternative splicing that give rise to different isoforms in nerve tissue that support cancer progression, growth and development have also been investigated. Finally, we discuss the potential of our knowledge in alternative splicing to improve tumor diagnosis and treatment.The South African Medical Research Council (SA-MRC)http://www.mdpi.com/journal/cancerspm2021SurgeryUrolog