scholarly journals Recent Advances in Oligonucleotide Therapeutics in Oncology

2021 ◽  
Vol 22 (7) ◽  
pp. 3295
Author(s):  
Haoyu Xiong ◽  
Rakesh N. Veedu ◽  
Sarah D. Diermeier
Keyword(s):  
Clinical Trials ◽  
Antisense Oligonucleotides ◽  
Causes Of Death ◽  
Survival Rates ◽  
Cancer Recurrence ◽  
Small Interfering Rnas ◽  
The Past ◽  
Oncology Review ◽  
Recent Developments ◽  
Review Current

Cancer is one of the leading causes of death worldwide. Conventional therapies, including surgery, radiation, and chemotherapy have achieved increased survival rates for many types of cancer over the past decades. However, cancer recurrence and/or metastasis to distant organs remain major challenges, resulting in a large, unmet clinical need. Oligonucleotide therapeutics, which include antisense oligonucleotides, small interfering RNAs, and aptamers, show promising clinical outcomes for disease indications such as Duchenne muscular dystrophy, familial amyloid neuropathies, and macular degeneration. While no approved oligonucleotide drug currently exists for any type of cancer, results obtained in preclinical studies and clinical trials are encouraging. Here, we provide an overview of recent developments in the field of oligonucleotide therapeutics in oncology, review current clinical trials, and discuss associated challenges.

scholarly journals Adjuvant Therapy for Melanoma: Past, Current, and Future Developments

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1994 ◽  
Author(s):  
Alessandro A. E. Testori ◽  
Silvia Chiellino ◽  
Alexander C.J. van Akkooi
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Adjuvant Therapy ◽  
Target Therapy ◽  
Survival Rates ◽  
Immune Checkpoint Blockade ◽  
Severe Toxicity ◽  
Toxic Side Effect ◽  
The Past ◽  
Melanoma Patients

This review describes the progress that the concept of adjuvant therapies has undergone in the last 50 years and focuses on the most recent development where an adjuvant approach has been scientifically evaluated in melanoma clinical trials. Over the past decade the development of immunotherapies and targeted therapies has drastically changed the treatment of stage IV melanoma patients. These successes led to trials studying the same therapies in the adjuvant setting, in high risk resected stage III and IV melanoma patients. Adjuvant immune checkpoint blockade with anti-CTLA-4 antibody ipilimumab was the first drug to show an improvement in recurrence-free and overall survival but this was accompanied by high severe toxicity rates. Therefore, these results were bypassed by adjuvant treatment with anti-PD-1 agents nivolumab and pembrolizumab and BRAF-directed target therapy, which showed even better recurrence-free survival rates with more favorable toxicity rates. The whole concept of adjuvant therapy may be integrated with the new neoadjuvant approaches that are under investigation through several clinical trials. However, there is still no data available on whether the effective adjuvant therapy that patients finally have at their disposal could be offered to them while waiting for recurrence, sparing at least 50% of them a potentially long-term toxic side effect but with the same rate of overall survival (OS). Adjuvant therapy for melanoma has radically changed over the past few years—anti-PD-1 or BRAF-directed therapy is the new standard of care.

scholarly journals Immunotherapy for pediatric brain tumors: past and present

2019 ◽  
Vol 21 (10) ◽  
pp. 1226-1238 ◽  
Author(s):  
Jessica B Foster ◽  
Peter J Madsen ◽  
Meenakshi Hegde ◽  
Nabil Ahmed ◽  
Kristina A Cole ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Tumors ◽  
Pediatric Brain Tumors ◽  
Adoptive T Cell Therapy ◽  
Active Immunotherapy ◽  
T Cell Therapy ◽  
The Past ◽  
Formidable Challenge ◽  
Recent Developments ◽  
Pediatric Brain

AbstractThe field of cancer immunotherapy has progressed at an accelerated rate over the past decade. Pediatric brain tumors thus far have presented a formidable challenge for immunotherapy development, given their typically low mutational burden, location behind the blood–brain barrier in a unique tumor microenvironment, and intratumoral heterogeneity. Despite these challenges, recent developments in the field have resulted in exciting preclinical evidence for various immunotherapies and multiple clinical trials. This work reviews the history and advances in active immunotherapy, checkpoint blockade, and adoptive T-cell therapy for pediatric brain tumors, including ongoing clinical trials.

scholarly journals A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020

2021 ◽  
Author(s):  
Gizem Kayki-Mutlu ◽  
Martin C. Michel
Keyword(s):  
Small Molecules ◽  
Drug Administration ◽  
Antisense Oligonucleotides ◽  
Food And Drug Administration ◽  
New Drugs ◽  
Small Interfering Rnas ◽  
Drug Discovery And Development ◽  
The Past ◽  
The Us ◽  
Approved Drugs

AbstractWhile the COVID-19 pandemic also affected the work of regulatory authorities, the US Food and Drug Administration approved a total of 53 new drugs in 2020, one of the highest numbers in the past decades. Most newly approved drugs related to oncology (34%) and neurology (15%). We discuss these new drugs by level of innovation they provide, i.e., first to treat a condition, first using a novel mechanisms of action, and “others.” Six drugs were first in indication, 15 first using a novel mechanism of action, and 32 other. This includes many drugs for the treatment of orphan indications and some for the treatment of tropical diseases previously neglected for commercial reasons. Small molecules continue to dominate new drug approvals, followed by antibodies. Of note, newly approved drugs also included small-interfering RNAs and antisense oligonucleotides. These data show that the trend for declines in drug discovery and development has clearly been broken.

scholarly journals T Cells and Adoptive Immunotherapy: Recent Developments and Future Prospects in Gastrointestinal Oncology

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Amedeo Amedei ◽  
Elena Niccolai ◽  
Mario M. D'Elios
Keyword(s):  
T Cells ◽  
Adoptive Immunotherapy ◽  
Causes Of Death ◽  
Specific Immunotherapy ◽  
Survival Rates ◽  
Tumor Resection ◽  
Gastrointestinal Cancers ◽  
Significant Progress ◽  
Recent Developments

Gastrointestinal oncology is one of the foremost causes of death: the gastric cancer accounts for 10.4% of cancer deaths worldwide, the pancreatic cancer for 6%, and finally, the colorectal cancer for 9% of all cancer-related deaths. For all these gastrointestinal cancers, surgical tumor resection remains the primary curative treatment, but the overall 5-year survival rate remains poor, ranging between 20–25%; the addition of combined modality strategies (pre- or postoperative chemoradiotherapy or perioperative chemotherapy) results in 5-year survival rates of only 30–35%. Therefore, many investigators believe that the potential for making significant progress lies on understanding and exploiting the molecular biology of gastrointestinal tumors to investigate new therapeutic strategies such as specific immunotherapy. In this paper we will focus on recent knowledge concerning the role of T cells and the use of T adoptive immunotherapy in the treatment of gastrointestinal cancers.

scholarly journals Making Sense of Antisense Oligonucleotide Therapeutics Targeting Bcl-2

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 97
Author(s):  
Maria Gagliardi ◽  
Ana Tari Ashizawa
Keyword(s):  
Clinical Trials ◽  
Cell Survival ◽  
Antisense Oligonucleotides ◽  
Target Gene ◽  
Cell Lymphoma ◽  
Chemotherapy Resistance ◽  
B Cell Lymphoma ◽  
The Past ◽  
Making Sense ◽  
Wide Range

The B-cell lymphoma 2 (Bcl-2) family, comprised of pro- and anti-apoptotic proteins, regulates the delicate balance between programmed cell death and cell survival. The Bcl-2 family is essential in the maintenance of tissue homeostasis, but also a key culprit in tumorigenesis. Anti-apoptotic Bcl-2, the founding member of this family, was discovered due to its dysregulated expression in non-Hodgkin’s lymphoma. Bcl-2 is a central protagonist in a wide range of human cancers, promoting cell survival, angiogenesis and chemotherapy resistance; this has prompted the development of Bcl-2-targeting drugs. Antisense oligonucleotides (ASO) are highly specific nucleic acid polymers used to modulate target gene expression. Over the past 25 years several Bcl-2 ASO have been developed in preclinical studies and explored in clinical trials. This review will describe the history and development of Bcl-2-targeted ASO; from initial attempts, optimizations, clinical trials undertaken and the promising candidates at hand.

scholarly journals The Limitless Future of RNA Therapeutics

2021 ◽  
Vol 9 ◽  
Author(s):  
Tulsi Ram Damase ◽  
Roman Sukhovershin ◽  
Christian Boada ◽  
Francesca Taraballi ◽  
Roderic I. Pettigrew ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Antisense Oligonucleotides ◽  
Messenger Rna ◽  
Cost Effective ◽  
Standard Of Care ◽  
Regulatory Approval ◽  
Cellular Delivery ◽  
Small Interfering Rnas ◽  
Broad Array

Recent advances in the generation, purification and cellular delivery of RNA have enabled development of RNA-based therapeutics for a broad array of applications. RNA therapeutics comprise a rapidly expanding category of drugs that will change the standard of care for many diseases and actualize personalized medicine. These drugs are cost effective, relatively simple to manufacture, and can target previously undruggable pathways. It is a disruptive therapeutic technology, as small biotech startups, as well as academic groups, can rapidly develop new and personalized RNA constructs. In this review we discuss general concepts of different classes of RNA-based therapeutics, including antisense oligonucleotides, aptamers, small interfering RNAs, microRNAs, and messenger RNA. Furthermore, we provide an overview of the RNA-based therapies that are currently being evaluated in clinical trials or have already received regulatory approval. The challenges and advantages associated with use of RNA-based drugs are also discussed along with various approaches for RNA delivery. In addition, we introduce a new concept of hospital-based RNA therapeutics and share our experience with establishing such a platform at Houston Methodist Hospital.

Wilfred Ethier. Modern International Economics. New York: W. W. Norton and Company. 1983. xviii + 588 pp.

1988 ◽  
Vol 27 (1) ◽  
pp. 81-83
Author(s):  
Nadeem A. Burney
Keyword(s):  
International Economic ◽  
New York ◽  
Economic Theory ◽  
International Economics ◽  
International Monetary System ◽  
International Markets ◽  
The Past ◽  
Monetary System ◽  
Recent Developments

Its been long recognized that various economies of the world are interlinked through international trade. The experience of the past several years, however, has demonstrated that this economic interdependence is far greater than was previously realized. In this context, the importance of international economic theory as an area distinct from general economics hardly needs any mentioning. What gives international economic theory this distinction is international markets for some goods and effects of national sovereignty on the character of economic activity. Wilfred Ethier's book, which incorporates recent developments in the field, is an excellent addition to textbooks on international economics for one- or twosemester undergraduate courses. The book mostly covers standard topics. A distinguishing feature of this book is its detailed analysis of the flexible exchange rates and a discussion of the various approaches used for their determination. Within each chapter, the author has extensively used facts, figures and major events to clarify the concepts in the light of the theoretical framework. The book also discusses, in a fair amount of detail, the existing international monetary system and the role of various international organizations.

Developments in sugarcane processing over the past 15 years

2019 ◽  
pp. 451-458
Author(s):  
Peter W. Rein
Keyword(s):  
Environmental Conditions ◽  
Energy Value ◽  
The Past ◽  
Recent Developments ◽  
Technology Of Production ◽  
Sugarcane Processing

Developments in the technology of production of sugar from sugarcane tend to be incremental improvements in an effort to reduce costs and boost revenue. Nonetheless the developments are significant and contribute to sustainable sugarcane enterprises. Some technologies have adapted to changing environmental conditions, and more attention is being given to boosting revenue through associated activities, particularly in enhancing the potential for sugarcane operations to exploit the energy value of sugarcane. This paper outlines recent developments of interest in processing sugarcane.

Performing States-Of-In-Between: Dogs, Parrots, and Other Humans in Recent Austrian Performances

2017 ◽  
Vol 40 (3) ◽  
pp. 295-310
Author(s):  
Sabine Wilke
Keyword(s):  
Fine Arts ◽  
Specific Form ◽  
Cultural Critique ◽  
Contemporary Society ◽  
Dramatic Effect ◽  
The Past ◽  
Violent Content ◽  
The World ◽  
The Sixties ◽  
Recent Developments

Every late spring since 1951, the Wiener Festwochen bring performers from around the world to Vienna for an opportunity to share recent developments in performance styles and present them to a Viennese public that seems to be increasingly open to experimentation. These festival weeks solidify a specific form of Viennese self-understanding and self-representation as a culture that is rooted in performance. This essay seeks to link two recent Austrian performances—one of them was part of the Wiener Festwochen in 2016, the other was staged in downtown Linz during the past few years—to this Austrian and specifically Viennese culture of performance by reading them as contemporary articulations of a tradition of radical performance art that can be traced back to the Viennese Actionism of the sixties and later feminist articulations in the seventies and eighties. They play on the dramatic effect of these actions, specifically their joy in cruelty, chaos, and orgiastic intoxication, by staging regressions and thus making visible what has been dammed up and repressed in contemporary society.1 Just as their historical models, these two performances merge the performing and the fine arts and they highlight provocative, controversial, and, at times, violent content. But they do it in an interspecies context that adds an entire layer of complexity to the project of societal and cultural critique.

The Medicinal Chemistry of Therapeutic Peptides: Recent Developments in Synthesis and Design Optimizations

2019 ◽  
Vol 26 (13) ◽  
pp. 2330-2355 ◽  
Author(s):  
Anutthaman Parthasarathy ◽  
Sasikala K. Anandamma ◽  
Karunakaran A. Kalesh
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
The Past ◽  
Recombinant Production ◽  
Tremendous Progress ◽  
Recent Developments ◽  
Therapeutic Peptides ◽  
Development Processes ◽  
Delivery Strategies

Peptide therapeutics has made tremendous progress in the past decade. Many of the inherent weaknesses of peptides which hampered their development as therapeutics are now more or less effectively tackled with recent scientific and technological advancements in integrated drug discovery settings. These include recent developments in synthetic organic chemistry, high-throughput recombinant production strategies, highresolution analytical methods, high-throughput screening options, ingenious drug delivery strategies and novel formulation preparations. Here, we will briefly describe the key methodologies and strategies used in the therapeutic peptide development processes with selected examples of the most recent developments in the field. The aim of this review is to highlight the viable options a medicinal chemist may consider in order to improve a specific pharmacological property of interest in a peptide lead entity and thereby rationally assess the therapeutic potential this class of molecules possesses while they are traditionally (and incorrectly) considered ‘undruggable’.

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