The repurposing of previously clinically approved drugs as an alternative therapeutic approach to treating disease has gained significant attention in recent years. A multitude of studies have demonstrated various and successful therapeutic interventions with these drugs in a wide range of neoplastic diseases, including multiple myeloma, leukaemia, glioblastoma, and colon cancer. Drug repurposing has been widely encouraged due to the known efficacy, safety, and convenience of already established drugs, allowing the bypass of the long and difficult road of lead optimization and drug development. Repurposing drugs in cancer therapy is an exciting prospect due to the ability of these drugs to successfully target cancer-associated genes, often dysregulated in oncogenic signalling pathways, amongst which are the classical cancer signalling pathways; WNT (wingless-related integration type) and Hippo signalling. These pathways play a fundamental role in controlling organ size, tissue homeostasis, cell proliferation, and apoptosis, all hallmarks of cancer initiation and progression. Prolonged dysregulation of these pathways has been found to promote uncontrolled cellular growth and malignant transformation, contributing to carcinogenesis and ultimately leading to malignancy. However, the translation of cancer signalling pathways and potential targeted therapies in cancer treatment faces ongoing challenges due to the pleiotropic nature of cancer cells, contributing to resistance and an increased rate of incomplete remission in patients. This review provides analyses of a range of potential anti-cancer compounds in drug repurposing. It unravels the current understanding of the molecular rationale for repurposing these drugs and their potential for targeting key oncogenic signalling pathways.

Female cancers such as breast and gynaecological cancers contribute to a significant global health burden and are a leading cause of fatality among women. With current treatment options often limited by resistance to cytotoxic drugs, side effects and lack of specificity to the cancer, there is a pressing need for alternative treatments. Recent research has highlighted the promising role of non-coding RNAs (ncRNA) in regulating these issues and providing more targeted approaches to suppressing key cancer pathways. This review explores the involvement of the various types of non-coding RNAs in regulating key oncogenic pathways, namely, the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin and p53 pathways, in a range of female cancers such as breast, cervical, ovarian and endometrial cancers. Evidence from a multitude of studies suggests that non-coding RNAs function as double-edged swords, serving as both oncogenes and tumour suppressors, depending on their expression and cellular interactions. By mapping and investigating these regulatory interactions, this review demonstrates the complexity and dual functionality of ncRNAs in cancer. Understanding these complex mechanisms is essential for the development of new and effective ncRNA-based diagnostic methods and targeted therapies in female cancer treatment.

Plant extracts are increasingly becoming an answer to expensive, high-dose, synthesized chemotherapy, with milder side effects and easier accessibility. Many botanical plants contain active ingredients, such as terpenoids and alkaloids, which may combat cancer; however, studies need to be performed to test whether they are solely effective enough and whether the extracted compounds are selective for the tumor itself. Many chemotherapy drugs were initially of botanical origin, such as vincristine from Catharanthus roseus and paclitaxel from the Taxus baccata tree. The objective of this review is to assess the mechanisms of herbal therapeutics in their role against malignancy. Ajwa, curcumin, ginseng, lycopene, and ursolic acid were all respectively evaluated in the paper for their prevalent properties, their method of extraction, notable usage in medicine, which pathways they activate, and whether the transductions can disrupt cancer formation or proliferation. The findings from the review demonstrated that all the therapeutics exhibited pro-apoptotic behavior, Ajwa and curcumin exerted cell cycle arrest upon neoplasms, and Ajwa, curcumin, and lycopene showed anti-metastatic behavior. Most extracts were tested on colorectal cancer, and the pathways most commonly applied were through BAX/Bcl2 and endoproteases, such as caspase-3 and caspase-9, indicating predominantly mitochondrial apoptosis. In addition, cell cycle arrest was noted to occur during the G2/M phase via Wnt/β-catenin in both curcumin and ginseng, independently of the Wnt/β-catenin pathway in Ajwa constituents, reducing cell viability. All of these studies were demonstrated in vitro within varieties of single cell cultures, which did not take into account bioavailability nor properly demonstrate the tumor microenvironment, which may not yield the same results in vivo. Clinical trials need to be undergone to appropriately test effective dosages, as if a compound is strongly pro-apoptotic, it may not be selective just to tumor cells but also to healthy cells, which may impair their functions.

Lipid metabolism plays a significant role in the regulation of various critical pathways within cells, where enhanced lipid metabolism is a hallmark of cancer cell metabolism. The Hippo signalling pathway poses as an important signalling pathway that governs tissue growth control and tumorigenesis. The effector of the Hippo signalling pathway, Yes-associated protein (YAP), serves as a central regulator for this growth control. Once a tissue develops to its correct size, YAP is phosphorylated and inactivated within the cytoplasm by the activation of the Hippo pathway, where its inactivation results in YAP nucleus translocation. This allows its dephosphorylation, modulating various cellular behaviours such as cellular proliferation and the inhibition of apoptosis. Moreover, it has been established that YAP is positively regulated by the extracellular matrix (ECM). The interplay between the Hippo signalling pathway, the ECM, and lipid metabolism, however, is not entirely clear. Thus, this study illustrates a novel link between the Hippo signalling pathway, the ECM, and lipid metabolism. Furthermore, the project identifies a novel ECM complex which is dependent upon lipids and regulates YAP in a positive manner.

Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumour, originating from glial cells known as astrocytes and accounting for over 50% of all central nervous system malignancies. Its aetiology is linked to various factors, including radiation exposure, genetic alterations, and viral influences, which trigger the uncontrolled growth and rapid infiltration of glial cells into surrounding brain tissues. Despite standard multidisciplinary management involving maximal safe surgical resection, radiotherapy, and temozolomide, the prognosis remains poor. The molecular landscape of GBM is characterised by profound dysregulation across highly conserved signalling networks, including the PI3K/AKT/mTOR, ERK/MAPK, Wnt/β-catenin, and Hippo pathways. These pathways are frequently hijacked by genetic and epigenetic alterations such as EGFR amplification and PTEN loss, which drive essential hallmarks of cancer like uncontrolled proliferation, angiogenesis, and apoptosis evasion. A defining feature of GBM is its extreme intra-tumoral heterogeneity and cellular plasticity, where tumour cells dynamically transition between distinct transcriptional states, including mesenchymal, astrocyte-like, and neural progenitor-like, to adapt to therapeutic pressures. This complexity is further exacerbated by microenvironmental factors. Clinical progress is severely hindered by the blood–brain barrier (BBB), which restricts systemic agents from reaching invasive tumour margins. Targeted monotherapies, such as EGFR and mTOR inhibitors, have largely failed in clinical trials due to compensatory feedback loops and pathway redundancy. Consequently, the therapeutic paradigm is shifting toward rational combination therapies and novel immunotherapeutic platforms. Emerging strategies, such as bivalent CAR T-cell therapy targeting both EGFRvIII and IL-13Rα2, have shown early clinical promise in achieving tumour regression, highlighting a potential path toward precision medicine. This review synthesises current insights into signalling dysregulation and explores the future frontiers of multi-targeted therapeutic interventions in GBM.