Cancers

Radiotherapy has been a central component of cancer therapy for over a century, with the field rapidly evolving over time, resulting in improved outcomes. These advances have contributed to a changing demographic, with growing numbers of people living longer with, and surviving the disease. This has been accompanied by an increasing burden of chronic physical and psychological side effects, including radiotherapy-related toxicity. These long-term consequences have a substantial impact on patients, their carers, and healthcare systems. Significant global inequities persist, particularly in low- and middle-income countries (LMICs), where access to radiotherapy and comprehensive supportive and palliative care remains limited. Supportive oncology has emerged as a new field focusing on the management of acute, chronic, and emergent problems in people living with and beyond cancer. Despite its benefits, palliative radiotherapy continues to be underused, especially in specific patient groups including paediatrics, older age adults, and those with a short prognosis. Often treatment decisions in these patient groups are challenging and the integration of supportive oncology could help overcome this. Furthermore, radiotherapy toxicity and its management has been under-researched despite huge advancements in cancer treatments leading to a lack of guidelines and varied practice globally. Supportive oncology offers a framework to address these challenges through earlier integration into treatment pathways, multidisciplinary collaboration, and a stronger focus on symptom control, survivorship, and equity. Embedding supportive oncology within radiotherapy services is essential to delivering high-quality, patient-centred cancer care worldwide.

Cervical cancer remains one of the most commonly diagnosed cancers in women worldwide, with an elevated number of associated annual deaths, even though effective preventive vaccines are available. The pathophysiology of cervical cancer is well understood, with high-risk HPV as the main culprit in carcinogenesis, in addition to cell proliferation signaling alteration and tumor immune microenvironment modulation. This understanding of the disease’s molecular signatures has led to the development of several lines of treatment, especially for advanced, recurrent, persistent, or metastatic disease. For instance, Bevacizumab, a monoclonal antibody targeting angiogenesis factors, as well as Endostar, a recombinant human endostatin, have been studied and shown to improve survival in advanced disease. In contrast, anti-angiogenic Tyrosine Kinase Inhibitors had limited efficacy. Furthermore, antibody-drug conjugates such as Tisotumab Vedotin allow to deliver a highly toxic payload directly to the tumor site by binding to tissue factor, which is highly expressed in cervical tumor cells. Moreover, immunotherapy has emerged as a key treatment modality in cervical cancer by inhibiting immune checkpoint inhibitors (PD1, PD-L1, and CTLA4). In addition, therapeutic vaccines have been investigated for the treatment of localized disease by enhancing cell-mediated immunity against E6 and E7 proteins. However, more robust clinical trials are needed before these vaccines can be effectively and safely used clinically. Finally, several ongoing trials are currently evaluating new therapeutic modalities and combinations of the currently available tools in the cervical cancer treatment armamentarium.

Background/Objectives: Repurposed cAMP-elevating agents may personalize fluoropyrimidine therapy by exploiting pathway-specific vulnerabilities. Methods: We tested the PDE3 inhibitor milrinone and the β2-agonist terbutaline alone or combined with 10 μM 5-fluorouracil (5-FU) in UM-UC-5 (bladder), A549 (lung), and PC-3 (prostate) cells. Viability, migration, clonogenicity, and intracellular ROS (DCFDA) were measured; drug interactions used Chou–Talalay/CompuSyn. Results: In UM-UC-5, both agents reduced viability, migration, and clonogenicity and synergized with 5-FU (CI < 1 across Fa ≈ 0.42–0.57). 5-FU increased ROS, whereas terbutaline consistently lowered ROS below baseline and blunted 5-FU-induced oxidative signals; milrinone showed a dose-dependent redox profile without consistent ROS suppression. A549 combinations did not outperform 5-FU; PC-3 was largely unresponsive. Conclusions: cAMP modulators selectively potentiate 5-FU in bladder cancer cells and modulate redox programs (notably with terbutaline), supporting a biomarker-guided combination strategy (e.g., β2-AR/PDE3/PI3K–Akt features) for personalized therapy in bladder cancer; mechanistic and in vivo validation are warranted.