scholarly journals Repurposing of α1-Adrenoceptor Antagonists: Impact in Renal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2442 ◽  
Author(s):  
Meredith Mihalopoulos ◽  
Zachary Dovey ◽  
Maddison Archer ◽  
Talia G. Korn ◽  
Kennedy E. Okhawere ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Metastatic Disease ◽  
Treatment Strategies ◽  
Metastatic Potential ◽  
Immune Checkpoint Blockade ◽  
Renal Tumors ◽  
Current Evidence ◽  
Anoikis Resistance ◽  
Mtor Inhibition ◽  
Novel Treatment Strategies

Renal cancer ranks twelfth in incidence among cancers worldwide. Despite improving outcomes due to better therapeutic options and strategies, prognosis for those with metastatic disease remains poor. Current systemic therapeutic approaches include inhibiting pathways of angiogenesis, immune checkpoint blockade, and mTOR inhibition, but inevitably resistance develops for those with metastatic disease, and novel treatment strategies are urgently needed. Emerging molecular and epidemiological evidence suggests that quinazoline-based α1-adrenoceptor-antagonists may have both chemopreventive and direct therapeutic actions in the treatment of urological cancers, including renal cancer. In human renal cancer cell models, quinazoline-based α1-adrenoceptor antagonists were shown to significantly reduce the invasion and metastatic potential of renal tumors by targeting focal adhesion survival signaling to induce anoikis. Mechanistically these drugs overcome anoikis resistance in tumor cells by targeting cell survival regulators AKT and FAK, disrupting integrin adhesion (α5β1 and α2β1) and engaging extracellular matrix (ECM)-associated tumor suppressors. In this review, we discuss the current evidence for the use of quinazoline-based α1-adrenoceptor antagonists as novel therapies for renal cell carcinoma (RCC) and highlight their potential therapeutic action through overcoming anoikis resistance of tumor epithelial and endothelial cells in metastatic RCC. These findings provide a platform for future studies that will retrospectively and prospectively test repurposing of quinazoline-based α1-adrenoceptor-antagonists for the treatment of advanced RCC and the prevention of metastasis in neoadjuvant, adjuvant, salvage and metastatic settings.

scholarly journals Antimicrobial Treatment Strategies for Stenotrophomonas maltophilia: A Focus on Novel Therapies

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1226
Author(s):  
Jean Gibb ◽  
Darren W. Wong
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Treatment Strategies ◽  
Antimicrobial Treatment ◽  
Current Evidence ◽  
Antibiotic Development ◽  
Carbapenem Resistant ◽  
Novel Treatment ◽  
Novel Treatment Strategies ◽  
Global Threat ◽  
Carbapenem Resistant Enterobacteriaceae

Stenotrophomonas maltophilia is an urgent global threat due to its increasing incidence and intrinsic antibiotic resistance. Antibiotic development has focused on carbapenem-resistant Enterobacteriaceae, Pseudomonas, and Acinetobacter, with approved antibiotics in recent years having limited activity for Stenotrophomonas. Accordingly, novel treatment strategies for Stenotrophomonas are desperately needed. We conducted a systemic literature review and offer recommendations based on current evidence for a treatment strategy of Stenotrophomonas infection.

scholarly journals Diagnostic Strategies for Treatment Selection in Advanced Prostate Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 345
Author(s):  
Ciara S. McNevin ◽  
Anne-Marie Baird ◽  
Ray McDermott ◽  
Stephen P. Finn
Keyword(s):  
Prostate Cancer ◽  
Treatment Strategies ◽  
Treatment Selection ◽  
High Rate ◽  
Current Evidence ◽  
Diagnostic Strategies ◽  
Novel Treatment ◽  
Proven Efficacy ◽  
Novel Treatment Strategies ◽  
Poor Outcomes

Prostate Cancer (PCa) is a leading cause of morbidity and mortality among men worldwide. For most men with PCa, their disease will follow an indolent course. However, advanced PCa is associated with poor outcomes. There has been an advent of new therapeutic options with proven efficacy for advanced PCa in the last decade which has improved survival outcomes for men with this disease. Despite this, advanced PCa continues to be associated with a high rate of death. There is a lack of strong evidence guiding the timing and sequence of these novel treatment strategies. This paper focuses on a review of the strategies for diagnostic and the current evidence available for treatment selection in advanced PCa.

scholarly journals Recent Developments in Treating Cognitive Impairment Associated with Schizophrenia

2021 ◽  
Author(s):  
Robert A Bittner ◽  
Catherine V Barnes-Scheufler ◽  
Meike D Hettwer ◽  
Andreas Reif ◽  
Mishal Qubad
Keyword(s):  
Cognitive Impairment ◽  
Neural Plasticity ◽  
Clinical Symptoms ◽  
Therapeutic Potential ◽  
Cognitive Impairments ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Potential Effect ◽  
Current Evidence ◽  
Novel Treatment Strategies

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

scholarly journals Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis

2021 ◽  
Vol 22 (5) ◽  
pp. 2778
Author(s):  
Mariam Markouli ◽  
Dimitrios Strepkos ◽  
Efthimia K. Basdra ◽  
Athanasios G. Papavassiliou ◽  
Christina Piperi
Keyword(s):  
Histone Modifications ◽  
Epithelial To Mesenchymal Transition ◽  
Treatment Strategies ◽  
Epigenetic Mechanisms ◽  
Anoikis Resistance ◽  
Post Translational Modifications ◽  
Mesenchymal Transition ◽  
Metastatic Process ◽  
Novel Treatment Strategies

Tumor aggressiveness and progression is highly dependent on the process of metastasis, regulated by the coordinated interplay of genetic and epigenetic mechanisms. Metastasis involves several steps of epithelial to mesenchymal transition (EMT), anoikis resistance, intra- and extravasation, and new tissue colonization. EMT is considered as the most critical process allowing cancer cells to switch their epithelial characteristics and acquire mesenchymal properties. Emerging evidence demonstrates that epigenetics mechanisms, DNA methylation, histone modifications, and non-coding RNAs participate in the widespread changes of gene expression that characterize the metastatic phenotype. At the chromatin level, active and repressive histone post-translational modifications (PTM) in association with pleiotropic transcription factors regulate pivotal genes involved in the initiation of the EMT process as well as in intravasation and anoikis resistance, playing a central role in the progression of tumors. Herein, we discuss the main epigenetic mechanisms associated with the different steps of metastatic process, focusing in particular on the prominent role of histone modifications and the modifying enzymes that mediate transcriptional regulation of genes associated with tumor progression. We further discuss the development of novel treatment strategies targeting the reversibility of histone modifications and highlight their importance in the future of cancer therapy.

scholarly journals Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

2021 ◽  
Author(s):  
Haoru Dong ◽  
Xinhua Shu ◽  
Qiang Xu ◽  
Chen Zhu ◽  
Andreas M. Kaufmann ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Head And Neck ◽  
Treatment Strategies ◽  
Hpv Infection ◽  
Immune Checkpoint Blockade ◽  
Current Status ◽  
Future Directions ◽  
Sequencing Technologies ◽  
E6 And E7 ◽  
The Continuum

AbstractHuman papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to 38%–80% of head and neck squamous cell carcinoma (HNSCC) in oropharyngeal location (OPSCC) and nearly all cervical cancers contain the HPV genome which is implicated in causing cancer through its oncoproteins E6 and E7. Given by the biologically distinct HPV-related OPSCC and a more favorable prognosis compared to HPV-negative tumors, clinical trials on de-escalation treatment strategies for these patients have been studied. It is therefore raised the questions for the patient stratification if treatment de-escalation is feasible. Moreover, understanding the crosstalk of HPV-mediated malignancy and immunity with clinical insights from the proportional response rate to immune checkpoint blockade treatments in patients with HNSCC is of importance to substantially improve the treatment efficacy. This review discusses the biology of HPV-related HNSCC as well as successful clinically findings with promising candidates in the pipeline for future directions. With the advent of various sequencing technologies, further biomolecules associated with HPV-related HNSCC progression are currently being identified to be used as potential biomarkers or targets for clinical decisions throughout the continuum of cancer care.

scholarly journals Novel Treatments and Technologies Applied to the Cure of Neuroblastoma

Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 482
Author(s):  
Irene Paraboschi ◽  
Laura Privitera ◽  
Gabriela Kramer-Marek ◽  
John Anderson ◽  
Stefano Giuliani
Keyword(s):  
Research Effort ◽  
Treatment Strategies ◽  
Adverse Outcomes ◽  
Treatment Protocols ◽  
Ongoing Research ◽  
Hematopoietic Stem ◽  
Novel Treatments ◽  
Therapeutic Modalities ◽  
High Risk Disease ◽  
Novel Treatment Strategies

Neuroblastoma (NB) is the most common extracranial solid tumour in childhood, accounting for approximately 15% of all cancer-related deaths in the paediatric population1. It is characterised by heterogeneous clinical behaviour in neonates and often adverse outcomes in toddlers. The overall survival of children with high-risk disease is around 40–50% despite the aggressive treatment protocols consisting of intensive chemotherapy, surgery, radiation therapy and hematopoietic stem cell transplantation2,3. There is an ongoing research effort to increase NB’s cellular and molecular biology knowledge to translate essential findings into novel treatment strategies. This review aims to address new therapeutic modalities emerging from preclinical studies offering a unique translational opportunity for NB treatment.

scholarly journals Immune Checkpoint Blockade in HER2-Positive Breast Cancer: What Role in Early Disease Setting?

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1655
Author(s):  
Cinzia Solinas ◽  
Debora Fumagalli ◽  
Maria Vittoria Dieci
Keyword(s):  
Breast Cancer ◽  
Immune Checkpoint ◽  
Neoadjuvant Treatment ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Current Evidence ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

The present commentary synthesizes the current evidence on the role of the immune response in HER2-positive breast cancer. It points out the strengths and weaknesses of the findings observed so far, particularly in the early setting, including the clinical significance of scoring tumor-infiltrating lymphocytes. A figure proposing research hypotheses for the implementation of immune checkpoint blockade use for patient candidates to neoadjuvant treatment is presented.

scholarly journals Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1371
Author(s):  
Justin Kwan ◽  
Uei Pua
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Treatment Strategies ◽  
Current Evidence ◽  
Unresectable Liver Metastasis ◽  
Hepatic Arterial Chemotherapy ◽  
Chemotherapy Infusion ◽  
Systemic Side Effects ◽  
Local Disease Control ◽  
Line Setting

The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy ‘holiday’ or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future.

scholarly journals Metabolic Interplay between the Immune System and Melanoma Cells: Therapeutic Implications

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 607
Author(s):  
Alice Indini ◽  
Francesco Grossi ◽  
Mario Mandalà ◽  
Daniela Taverna ◽  
Valentina Audrito
Keyword(s):  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Treatment Resistance ◽  
Metastatic Potential ◽  
Biological Behavior ◽  
Therapeutic Implications ◽  
Systemic Treatments

Malignant melanoma represents the most fatal skin cancer due to its aggressive biological behavior and high metastatic potential. Treatment strategies for advanced disease have dramatically changed over the last years due to the introduction of BRAF/MEK inhibitors and immunotherapy. However, many patients either display primary (i.e., innate) or eventually develop secondary (i.e., acquired) resistance to systemic treatments. Treatment resistance depends on multiple mechanisms driven by a set of rewiring processes, which involve cancer metabolism, epigenetic, gene expression, and interactions within the tumor microenvironment. Prognostic and predictive biomarkers are needed to guide patients’ selection and treatment decisions. Indeed, there are no recognized clinical or biological characteristics that identify which patients will benefit more from available treatments, but several biomarkers have been studied with promising preliminary results. In this review, we will summarize novel tumor metabolic pathways and tumor-host metabolic crosstalk mechanisms leading to melanoma progression and drug resistance, with an overview on their translational potential as novel therapeutic targets.

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