Emerging research demonstrates that co-inhibitory immune checkpoints (ICs) remain the most promising immunotherapy targets in various malignancies. Nonetheless, ICIs have offered insignificant clinical benefits in the treatment of advanced prostate cancer (PCa) especially when they are used as monotherapies. Current existing PCa treatment initially offers an improved clinical outcome and overall survival (OS), however, after a while the treatment becomes resistant leading to aggressive and uncontrolled disease associated with increased mortality and morbidity. Concurrent combination of the ICIs with radionuclides therapy that has rapidly emerged as safe and effective targeted approach for treating PCa patients may shift the paradigm of PCa treatment. Here, we provide an overview of the contextual contribution of old and new emerging inhibitory ICs in PCa, preclinical and clinical studies supporting the use of these ICs in treating PCa patients. Furthermore, we will also describe the potential of using a combinatory approach of ICIs and radionuclides therapy in treating PCa patients to enhance efficacy, durable cancer control and OS. The inhibitory ICs considered in this review are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1), V-domain immunoglobulin suppressor of T cell activation (VISTA), indoleamine 2,3-dioxygenase (IDO), T cell Immunoglobulin Domain and Mucin Domain 3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), B7 homolog 3 (B7-H3) and B7-H4.

Ionising radiation (IR) is a form of energy that travels as electromagnetic waves or particles. While it is vital in medical and occupational health settings, IR can also damage DNA, leading to mutations, chromosomal aberrations, and transcriptional changes that disrupt the functions of certain cell regulators, genes, and transcription factors. These disruptions can alter functions critical for cancer development, progression, and treatment response. Additionally, IR can affect various cellular proteins and their regulators within different cell signalling pathways, resulting in physiological changes that may promote cancer development, progression, and resistance to treatment. Understanding these impacts is crucial for developing strategies to mitigate the harmful effects of IR exposure and improve cancer treatment outcomes. This review focuses on specific genes and protein biomarkers regulated in response to chronic IR exposure, and how their regulation impacts disease onset, progression, and treatment response.

Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional “PARP enzyme–inhibitor complex” leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as breast cancer-associated gene (BRCA1/2). Hence, identifying HR-deficiencies by genomic analysis—for instance, BRCA1/2 used in triple-negative breast cancer—should be a part of the selection process for PARP inhibitor therapy. Published data suggest BRCA1/2 germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available BRCA1/2 analysis. In this review, we discuss [¹⁸F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.

Patients with cancer are presumed to be vulnerable to an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe clinical outcomes due to the immunocompromised state mediated by their underlying malignancies and therapy. The aim of this study was to estimate the SARS-CoV-2 seroprevalence, following second to fourth waves in solid tumour patients attending the Steve Biko Academic Hospital (SBAH) for diagnosis and treatment of cancer. We used the single-prick COVID-19 IgG/IgM Rapid Test Cassettes to detect SARS-CoV-2 IgG/IgM antibodies in 760 patients with solid tumours who were asymptomatic and who had never tested positive for coronavirus disease 2019 (COVID-19). Out of the 760 patients, 277 were male (36.4%), 483 were female (63.6%), and the mean age was 55 years (range 18–92). The estimated total seroprevalence was 33.2%. The seroprevalence status of the COVID-19 IgG/IgM antibodies rose significantly from the second wave (11.3%) to the third (67.38%) and then the fourth (69.81%) waves with roughly similar counts. A significant number of the seropositive patients were asymptomatic to COVID-19 (96%). There was a higher rate of seropositivity in cancer patients with hypertension (p < 0.05). Patients with breast, gynaecologic, and prostate cancers exhibited increased SARS-CoV-2 seropositivity. Although oncology patients may be susceptible to SARS-CoV-2 infection, our data indicate that these patients remained asymptomatic throughout various waves with an overall COVID-19 IgG/IgM antibody seropositivity of 33.16%, suggesting no risk of severe or fatal cases of COVID-19.

The overactivation of NRF2 (Nuclear factor erythroid 2-related factor 2) in female malignancies is an emerging field of study with significant implications for treatment efficacy. NRF2 plays a pivotal role in managing inflammation-induced oxidative stress, which is crucial components of the tumor microenvironment. Acting as a transcription factor and basic leucine zipper protein, it regulates the expression of various antioxidant genes that safeguard cells from oxidative stress and damage. While NRF2 activation is beneficial for the survival of normal cells, its overactivation in cancer cells can enhance tumor cell survival, proliferation, and resistance to treatments. Importantly, NRF2 has a dual context-dependent role, functioning as a tumor suppressor when transiently activated in normal cells to prevent carcinogenesis, but as an oncogene when persistently activated in established tumors. Understanding NRF2’s transcriptional alterations and developing targeted therapies could improve cancer management, prognosis and treatment outcomes, making it a promising target for precision oncology. This review aims to provide a comprehensive overview of NRF2 activation in female malignancies, including cervical, endometrial, ovarian, vaginal, vulvar and, breast cancers, and its association with chemoresistance, highlighting challenges and opportunities for developing more effective cancer treatments.

Oncogenic viruses typically manipulate host cellular mechanisms to drive tumorigenesis. They exploit pioneering transcription factors to modify gene expression, enabling uncontrolled proliferation. These viruses alter chromatin accessibility and induce chromatin remodelling, disrupting DNA repair and promoting viral genome integration. Additionally, epigenetic reprogramming through mechanisms like DNA methylation and histone modifications silences tumor suppressor genes and activates oncogenes. Understanding these mechanisms is critical for identifying more improved therapeutic targets, improving diagnostics, and predicting disease progression. Advances in this field can guide the development of innovative treatments and early detection tools. This comprehensive review synthesizes existing knowledge on the contributions of oncogenic viruses such as hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), and human T-cell leukaemia virus type 1 (HTLV-1), Epstein–Barr virus (EBV), human herpesvirus 8 (HHV-8), and Merkel cell polyomavirus (MCV) to cancer development, highlighting their therapeutic relevance and driving forward research in viral oncogenesis.