Bladder neoplasms, including the most common urothelial carcinoma, have been an escalating problem for years, especially in highly developed countries. Recent decades have brought us a steadily growing share of this cancer in terms of both morbidity and mortality statistics. Bladder neoplasms are not only a therapeutic challenge but also an economical one due to the demanding, costly diagnostics and treatment. The treatment of urothelial cancer can be divided depending on the stage and advancement; thus, we can distinguish three main categories: non-muscle invasive bladder cancer, conventionally treated by surgical interventions; muscle invasive bladder cancer, conventionally treated with chemotherapeutics; and advanced bladder cancer with distant metastases, conventionally treated with the intensive chemotherapy in the MVAC scheme (methotrexate, vinblastine, doxorubicin, and cisplatin). Recent years have brought a breakthrough: immunotherapy and targeted therapy were discovered to be beneficial for patients disqualified from chemotherapy or patients who progressed despite treatment. This literature review summarizes the latest research into the use of targeted therapy in the treatment of advanced bladder cancer, its benefits, and its limitations.
Basal cell carcinoma (BCC) is one of the most common neoplasms in the population. A good prognosis and mainly non-aggressive development have made it underdiagnosed and excluded from the statistics. Due to the availability of efficient surgical therapy, BCC is sometimes overlooked in the search for novel therapies. Most clinicians are unaware of its complicated pathogenesis or the availability of effective targeted therapy based on Hedgehog inhibitors (HHI) used in advanced or metastatic cases. Nevertheless, the concomitance and esthetic burden of this neoplasm are severe. As with other cancers, its pathogenesis is multifactorial and complicated with a network of dependencies. Although the tumour microenvironment (TME), genetic aberrations, and risk factors seem crucial in all skin cancers, in BCC they all have become accessible as therapeutic or prevention targets. The results of this review indicate that a central role in the development of BCC is played by the Hedgehog (Hh) signalling pathway. Two signalling molecules have been identified as the main culprits, namely Patched homologue 1 (PTCH1) and, less often, Smoothened homologue (SMO). Considering effective immunotherapy for other neoplastic growths being introduced, implementing immunotherapy in advanced BCC is pivotal and beneficial. Up to now, the US Food and Drug Administration (FDA) has approved two inhibitors of SMO for the treatment of advanced BCC. Sonidegib and vismodegib are registered based on their efficacy in clinical trials. However, despite this success, limitations might occur during the therapy, as some patients show resistance to these molecules. This review aims to summarize novel options of targeted therapies in BCC and debate the mechanisms and clinical implications of tumor resistance.
Cholangiocarcinomas (CCAs) are rare but aggressive tumours with poor diagnosis and limited treatment options. Molecular targeted therapies became a promising proposal for patients after progression under first-line chemical treatment. In light of an escalating prevalence of CCA, it is crucial to fully comprehend its pathophysiology, aetiology, and possible targets in therapy. Such knowledge would play a pivotal role in searching for new therapeutic approaches concerning diseases’ symptoms and their underlying causes. Growing evidence showed that fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) pathway dysregulation is involved in a variety of processes during embryonic development and homeostasis as well as tumorigenesis. CCA is known for its close correlation with the FGF/FGFR pathway and targeting this axis has been proposed in treatment guidelines. Bearing in mind the significance of molecular targeted therapies in different neoplasms, it seems most reasonable to move towards intensive research and testing on these in the case of CCA. However, there is still a need for more data covering this topic. Although positive results of many pre-clinical and clinical studies are discussed in this review, many difficulties lie ahead. Furthermore, this review presents up-to-date literature regarding the outcomes of the latest clinical data and discussion over future directions of FGFR-directed therapies in patients with CCA.
While gastrointestinal tumors remain a multifactorial and prevalent group of malignancies commonly treated surgically in combination with chemotherapy and radiotherapy, advancements regarding immunotherapeutic approaches continue to occur. Entering a new era of immunotherapy focused on overcoming resistance to preceding therapies caused the emergence of new therapeutic strategies. A promising solution surfaces with a V-domain Ig suppressor of T-cell activation (VISTA), a negative regulator of a T-cell function expressed in hematopoietic cells. Due to VISTA’s ability to act as both a ligand and a receptor, several therapeutic approaches can be potentially developed. A broad expression of VISTA was discovered on various tumor-growth-controlling cells, which proved to increase in specific tumor microenvironment (TME) conditions, thus serving as a rationale behind the development of new VISTA-targeting. Nevertheless, VISTA’s ligands and signaling pathways are still not fully understood. The uncertain results of clinical trials suggest the need for future examining inhibitor agents for VISTA and implicating a double immunotherapeutic blockade. However, more research is needed before the breakthrough can be achieved. This review discusses perspectives and novel approaches presented in the current literature. Based on the results of the ongoing studies, VISTA might be considered a potential target in combined therapy, especially for treating gastrointestinal malignancies.
Introduction and purpose Allergic rhinitis (AR) is a widely prevalent condition which affects mainly children. The disease is not as severe as other allergic disorders; however, its symptoms significantly impact the patient's quality of life. The therapeutic options have limited effectiveness and they are burdened with numerous side effects. In addition, AR’s underlying causes are not fully elucidated; thus, there is an urgent need to conduct more large sample studies on this topic. State of knowledge In recent years, research concerning the role of vitamin deficiency in AR pathogenesis gathered pace. Some studies report that children with vitamin A, C and D deficiencies more often suffer from allergic diseases, especially AR and asthma. Furthermore, they are more likely to have severe infections and other disorders caused by immune imbalance. The crucial aspect of vitamins' role in AR is their significant ability to modulate the immune response, especially adaptive, by restoring Th1/Th2 balance. Recent publications reported that vitamin supplementation in AR patients results in an improved clinical course of the disease and restored immune balance. Moreover, vitamins added to the typical treatment improve its effects. Conclusions This review aims to summarize the state of knowledge about the role of vitamin A, C and D deficiency in the pathogenesis of AR. Moreover, we point out the values of education in the field of proper dietary habits among AR patients. In addition, the effects of vitamin supplementation in AR patients are also emphasized.
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