Abstract Context Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and ...Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. Objective To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. Evidence acquisition An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. Evidence synthesis Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. Conclusions The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. Patient summary Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with metastatic and muscle-invasive bladder cancer.
Therapeutic ultrasound strategies that harness the mechanical activity of cavitation nuclei for beneficial tissue bio-effects are actively under development. The mechanical oscillations of ...circulating microbubbles, the most widely investigated cavitation nuclei, which may also encapsulate or shield a therapeutic agent in the bloodstream, trigger and promote localized uptake. Oscillating microbubbles can create stresses either on nearby tissue or in surrounding fluid to enhance drug penetration and efficacy in the brain, spinal cord, vasculature, immune system, biofilm or tumors. This review summarizes recent investigations that have elucidated interactions of ultrasound and cavitation nuclei with cells, the treatment of tumors, immunotherapy, the blood–brain and blood–spinal cord barriers, sonothrombolysis, cardiovascular drug delivery and sonobactericide. In particular, an overview of salient ultrasound features, drug delivery vehicles, therapeutic transport routes and pre-clinical and clinical studies is provided. Successful implementation of ultrasound and cavitation nuclei-mediated drug delivery has the potential to change the way drugs are administered systemically, resulting in more effective therapeutics and less-invasive treatments.
New therapies that promote antitumour immunity have been recently developed. Most of these immunomodulatory approaches have focused on enhancing T-cell responses, either by targeting inhibitory ...pathways with immune checkpoint inhibitors, or by targeting activating pathways, as with chimeric antigen receptor T cells or bispecific antibodies. Although these therapies have led to unprecedented successes, only a minority of patients with cancer benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in the next generation of immunotherapy. Given the crucial role of innate immune responses in immunity, harnessing these responses opens up new possibilities for long-lasting, multilayered tumour control.
Residual cancer after induction therapy for HER2-positive breast cancer is associated with a worse prognosis than no residual cancer. In a randomized trial, trastuzumab emtansine was superior to ...trastuzumab with respect to invasive disease–free survival.
Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis and metabolic rewiring are well-established drivers of breast cancer aggressiveness, therapy resistance, and poor ...prognosis. Targeting of HIF and its downstream targets in angiogenesis and metabolism has been unsuccessful so far in the breast cancer clinical setting, with major unresolved challenges residing in target selection, development of robust biomarkers for response prediction, and understanding and harnessing of escape mechanisms. This Review discusses the pathophysiological role of HIFs, angiogenesis, and metabolism in breast cancer and the challenges of targeting these features in patients with breast cancer. Rational therapeutic combinations, especially with immunotherapy and endocrine therapy, seem most promising in the clinical exploitation of the intricate interplay of HIFs, angiogenesis, and metabolism in breast cancer cells and the tumor microenvironment.
MXenes, an emerging family of graphene-analogues two-dimensional (2D) materials, have attracted continuous and tremendous attention in many application fields because of their intrinsic ...physiochemical properties and high performance in versatile applications. In this work, we report on the construction of tantalum carbide (Ta4C3) MXene-based composite nanosheets for multiple imaging-guided photothermal tumor ablation, which has been achieved by rational choice of the composition of MXenes and their surface functionalization. A redox reaction was activated on the surface of tantalum carbide (Ta4C3) MXene for in situ growth of manganese oxide nanoparticles (MnO x /Ta4C3) based on the reducing surface of the nanosheets. The tantalum components of MnO x /Ta4C3 acted as the high-performance contrast agents for contrast-enhanced computed tomography, and the integrated MnO x component functionalized as the tumor microenvironment-responsive contrast agents for T 1-weighted magnetic resonance imaging. The photothermal-conversion performance of MnO x /Ta4C3 composite nanosheets not only has achieved contrast-enhanced photoacoustic imaging, but also realized the significant tumor-growth suppression by photothermal hyperthermia. This work broadens the biomedical applications of MXenes, not only by the fabrication of family members of biocompatible MXenes, but also by the development of functionalization strategies of MXenes for cancer-theranostic applications.
In less than 10 years, melanoma treatment has been revolutionized with the approval of tyrosine kinase inhibitors and immune checkpoint inhibitors, which have been shown to have a significant impact ...on the prognosis of patients with melanoma. The early steps of this transformation have taken place in research laboratories. The mitogen‑activated protein kinase (MAPK) pathway, phosphoinositol‑3‑kinase (PI3K) pathway promote the development of melanoma through numerous genomic alterations on different components of these pathways. Moreover, melanoma cells deeply interact with the tumor microenvironment and the immune system. This knowledge has led to the identification of novel therapeutic targets and treatment strategies. In this review, the epidemiological features of cutaneous melanoma along with the biological mechanisms involved in its development and progression are summarized. The current state‑of‑the‑art of advanced stage melanoma treatment strategies and the currently available evidence of the use of predictive and prognostic biomarkers are also discussed.
The presence of distant metastases from differentiated thyroid carcinoma decreases the 10-year survival of patients by 50%. Bone metastases represent a frequent complication especially of follicular ...thyroid cancer and severely reduce the quality of life causing pain, fractures, and spinal cord compression. Diagnosis is established by correlating clinical suspicion with imaging. Imaging is essential to detect, localize, and assess the extension of the lesions and should be used in conjunction with clinical evidence. Bone metastases are typically associated with elevated markers of bone turnover, but these markers have not been evaluated in differentiated thyroid cancer. Skeletal and whole-body magnetic resonance imaging and fusion 2-deoxy-2-18Ffluoro-d-glucose whole-body positron emission tomography/computed tomography (PET/CT) are the best anatomic and functional imaging techniques available in specialized centers. For well-differentiated lesions, iodine-PET scan combined 124I-PET/CT is the newest imaging development and 131I is the first line of treatment. Bisphosphonates reduce the complications rate and pain, alone or in combination with radioiodine, radionuclides, or external beam radiotherapy and should be employed. Surgery and novel minimally invasive consolidation techniques demand an appropriate patient selection for best results on a multimodal approach. Basic research on interactions between tumor cells and bone microenvironment are identifying potential novel targets for future more effective therapeutic interventions for less differentiated tumors.
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