scholarly journals Therapeutic Application of Monoclonal Antibodies in Pancreatic Cancer: Advances, Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1781
Author(s):  
Gustavo A. Arias-Pinilla ◽  
Helmout Modjtahedi
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibodies ◽  
Antibody Therapy ◽  
Therapeutic Targets ◽  
Poor Response ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Western World ◽  
Wide Range ◽  
Novel Therapeutic

Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.

P1 Receptor Agonists/Antagonists in Clinical Trials - Potential Drug Candidates of the Future

2019 ◽  
Vol 25 (26) ◽  
pp. 2792-2807 ◽  
Author(s):  
Pobitra Borah ◽  
Satyendra Deka ◽  
Raghu Prasad Mailavaram ◽  
Pran Kishore Deb
Keyword(s):  
Clinical Trials ◽  
Biological Activities ◽  
Therapeutic Agents ◽  
Current Status ◽  
Preclinical Studies ◽  
P1 Receptors ◽  
Drug Candidates ◽  
Wide Range ◽  
P1 Receptor ◽  
Novel Therapeutic

Background: Adenosine mediates various physiological and pathological conditions by acting on its four P1 receptors (A1, A2A, A2B and A3 receptors). Omnipresence of P1 receptors and their activation, exert a wide range of biological activities. Thus, its modulation is implicated in various disorders like Parkinson’s disease, asthma, cardiovascular disorders, cancer etc. Hence these receptors have become an interesting target for the researchers to develop potential therapeutic agents. Number of molecules were designed and developed in the past few years and evaluated for their efficacy in various disease conditions. Objective: The main objective is to provide an overview of new chemical entities which have crossed preclinical studies and reached clinical trials stage following their current status and future prospective. Methods: In this review we discuss current status of the drug candidates which have undergone clinical trials and their prospects. Results: Many chemical entities targeting various subtypes of P1 receptors are patented; twenty of them have crossed preclinical studies and reached clinical trials stage. Two of them viz adenosine and regadenoson are approved by the Food and Drug Administration. Conclusion: This review is an attempt to highlight the current status, progress and probable future of P1 receptor ligands which are under clinical trials as promising novel therapeutic agents and the direction in which research should proceed with a view to come out with novel therapeutic agents.

Cancer immunology

2019 ◽  
pp. 330-343
Author(s):  
Herman Waldmann
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tumour Microenvironment ◽  
Therapeutic Strategies ◽  
Self Tolerance ◽  
Wide Range ◽  
Tumour Antigens ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Until recently, the prospects for harnessing immune mechanisms to fight cancer were not encouraging. The advent of monoclonal antibodies, both as diagnostics and as probes for molecular function, have been important, while the identification of dendritic cells as a major intermediary between the antigen source and T-cell activation has been crucial. Major advances in molecular biology and the creation of mutant mice lacking defined gene products have pinpointed key molecules influencing immune function. Finally, many translational efforts in vaccination, autoimmune disease, and transplantation have enabled identification of hitherto undervalued mechanisms that the immune system uses to regulate itself. A fuller understanding of self-tolerance mechanisms, tumour antigens, and the tumour microenvironment has catalysed a wide range of novel therapeutic strategies and has also allowed a re-evaluation of mechanisms underlying the benefits of past chemotherapies.

scholarly journals Double-Headed Cationic Lipopeptides: An Emerging Class of Antimicrobials

2020 ◽  
Vol 21 (23) ◽  
pp. 8944
Author(s):  
Izabela Małuch ◽  
Oktawian Stachurski ◽  
Paulina Kosikowska-Adamus ◽  
Marta Makowska ◽  
Marta Bauer ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fungal Infections ◽  
Therapeutic Agents ◽  
Peptide Sequence ◽  
Side Chain ◽  
Biological Functions ◽  
Promising Tool ◽  
Self Assembling ◽  
Wide Range ◽  
Novel Therapeutic

Antimicrobial peptides (AMPs) constitute a promising tool in the development of novel therapeutic agents useful in a wide range of bacterial and fungal infections. Among the modifications improving pharmacokinetic and pharmacodynamic characteristics of natural AMPs, an important role is played by lipidation. This study focuses on the newly designed and synthesized lipopeptides containing multiple Lys residues or their shorter homologues with palmitic acid (C16) attached to the side chain of a residue located in the center of the peptide sequence. The approach resulted in the development of lipopeptides representing a model of surfactants with two polar headgroups. The aim of this study is to explain how variations in the length of the peptide chain or the hydrocarbon side chain of an amino acid residue modified with C16, affect biological functions of lipopeptides, their self-assembling propensity, and their mode of action.

scholarly journals Current and Emerging Therapies for Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1247
Author(s):  
Iván Henríquez ◽  
Mack Roach ◽  
Todd M. Morgan ◽  
Alberto Bossi ◽  
Junior A. Gómez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Therapeutic Agents ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Landscape ◽  
Emerging Therapies ◽  
Wide Range ◽  
Risk Of Progression ◽  
Novel Therapeutic

Metastatic castration-resistant prostate cancer (mCRPC) encompasses a heterogeneous wide range of molecular tumor behavior and a high risk of progression. Early detection and treatment are therefore crucial in these patients. Treatment has improved drastically in recent years and many novel therapeutic agents are currently under investigation. However, due to the rapidly changing therapeutic landscape in mCRPC, it is difficult for clinicians to keep up to date with the latest innovations in this area. In the present narrative review, we discuss the current and emerging therapies for mCRPC as well as the clinical and molecular factors that can help predict which patients are most likely to benefit from these novel agents.

Identification of Novel Therapeutic Targets in Atm-Deficient Lymphomas Using a Whole Genome CRISPR/CAS-9 Screen

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1504-1504
Author(s):  
Tatjana Stankovic ◽  
Nicholas Davies ◽  
Louise J Tee ◽  
Andrew D Beggs ◽  
Malcolm Taylor
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Therapeutic Targets ◽  
B Cell Lymphoma ◽  
Tumour Cells ◽  
Drop Out ◽  
Genome Wide ◽  
Wide Range ◽  
Novel Therapeutic

ATM is a principal DNA damage response protein that synchronises a complex network of cellular responses to double stranded DNA breaks. ATM gene is recurrently mutated in a wide range of lymphoid malignancies, including B-cell chronic lymphocytic leukemia (CLL), T-prolymphocytic leukaemia (T-PLL), mantle cell lymphoma (MCL) and diffuse B cell lymphoma (DLBCL). ATM pathway is utilized by many DNA damaging agents and consequently inactivation of this pathway can lead to chemoresistance. Furthermore, in the absence of ATM tumour cells exhibit genomic instability that can lead to clonal selection and evolution even under current targeted treatments. Consequently there is clear need to understand dependency pathways in ATM-deficient tumours and apply tailored targeted therapies that will specifically eliminate those tumour cells. We have previously presented a novel murine model of ATM-deficiency that spontaneously generate lymphoid tumours, mostly DLBCL. These tumours have been successfully propagated both in recipient mice and in vitro, where several cell lines have been generated. Genome editing methods, such as CRISPR/CAS-9, permit the targeted disruption of specific genes. Protocols for genome wide screens have been developed based on this technology which can be used to identify genes that are essential for cellular survival. As such, these screens can be used to identify dependency pathways for tumours with specific genetic lesions. Using lentiviral transduction we established two cell lines that stably expressed CAS-9. We then performed a genome wide CRISPR screen using the GeCKO library to identify novel therapeutic targets in these Atm-deficient tumours. This library consists of 130,209 unique single guide RNA (sgRNAs), targetting 20,611 genes including 1176 miRNAs. A comparative analysis was performed of sgRNA drop-out following 15 cellular doublings. This revealed a number of pathways including those already known to be synthetically lethal with ATM deficiency, such as ATR and PARP. Pathway analysis of the top genes from this drop-out analysis identified oxidative phosphorylation, the spliceosome, ribosome biogenesis, N-glycan biosynthesis, pyrimidine metabolism and purine metabolism as the most significantly affected pathways. Furthermore, the drop-out screen revealed a number of miRNAs, including MiR-3470a, Mir-3971, MiR-669f and MiR-719. These data provide a unique molecular assessment of the dependency of ATM-deficient lymphomas and provide a number of novel putative therapeutic targets for treating such tumours. Disclosures No relevant conflicts of interest to declare.

Update on Targeted Therapy—Focus on Monoclonal Antibodies

2008 ◽  
Vol 21 (1) ◽  
pp. 4-16 ◽  
Author(s):  
Meredith B. Toma ◽  
Patrick J. Medina
Keyword(s):  
Monoclonal Antibody ◽  
Cell Death ◽  
Monoclonal Antibodies ◽  
Targeted Therapy ◽  
Antibody Therapy ◽  
Therapeutic Agents ◽  
Monoclonal Antibody Therapy ◽  
Effective Management ◽  
Cellular Targets ◽  
Common Structure

Monoclonal antibodies represent a diverse class of therapeutic agents frequently used in the treatment of various malignancies. Monoclonal antibodies have a common structure with varying amounts of human and nonhuman components. These agents have been developed to identify and to interact with specific cellular targets or signaling pathways, leading to cell death by various mechanisms. Adverse effects associated with monoclonal antibodies are related to their structure (human vs nonhuman content) and to their cellular targets. Pharmacists should be familiar with this class of therapeutic agents to provide effective management and to monitor patients receiving monoclonal antibody therapy.

scholarly journals Toll-Like Receptors as Novel Therapeutic Targets for the Treatment of Pancreatic Cancer

10.5772/27263 ◽  
2012 ◽  
Author(s):  
Kelly D. ◽  
Fabian Benencia ◽  
Leonard D. ◽  
Ramiro Malgor ◽  
Anthony Schwartz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Targets ◽  
Toll Like Receptors ◽  
Novel Therapeutic

Advances in the Management of Acute Venous Thromboembolism and New Therapeutic Agents

2021 ◽  
Author(s):  
Hannah Stevens ◽  
James McFadyen ◽  
Noel Chan
Keyword(s):  
Venous Thromboembolism ◽  
Unmet Needs ◽  
Therapeutic Targets ◽  
Therapeutic Agents ◽  
Narrative Review ◽  
Changing Practice ◽  
Recent Advances ◽  
Acute Venous Thromboembolism ◽  
Novel Therapeutic

AbstractImportant advances in the understanding and management of venous thromboembolism (VTE) have enhanced our ability to diagnose, prevent, and treat VTE. In this narrative review, we discuss how recent advances in the understanding and management of VTE are changing practice, highlight ongoing unmet needs in VTE management, and outline how novel therapeutic targets with little or no influence on hemostasis may help address these unmet needs.

Sign in / Sign up

Export Citation Format

Share Document