Knowledge-based Pharmcodynamics Biomarkers Implementation Using Commercially Available Databases in Early-stage Clinical Trials

Abstract The results of recent clinical trials for the management of limited-stage Hodgkin lymphoma have led to considerable debate, especially regarding the role of radiation therapy. This review highlights those recent trials and provides perspectives regarding their interpretation from a radiation oncologist and a hematologist. The trial protocol is available at http://www.nejm.org/doi/suppl/10.1056/NEJMoa1111961/suppl_file/nejmoa1111961_protocol.pdf.

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Patients With Early-Stage Breast Cancer Who Are Unrepresented in Clinical Trials Face Increased Mortality

Default Digital Object Group ◽

10.1200/adn.21.200742 ◽

2021 ◽

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Early Stage ◽

Early Stage Breast Cancer

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Emergence of Nanotechnology to Fight HIV Sexual Transmission: The Trip of G2-S16 Polyanionic Carbosilane Dendrimer to Possible Pre-Clinical Trials

International Journal of Molecular Sciences ◽

10.3390/ijms21249403 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9403

Author(s):

Ignacio Relaño-Rodríguez ◽

Maria Ángeles Muñoz-Fernández

Keyword(s):

Clinical Trials ◽

Histopathological Examination ◽

Early Stage ◽

Sexual Transmission ◽

Reaction Times ◽

Vaginal Mucosa ◽

Carbosilane Dendrimer ◽

Anti Hiv

Development of new, safe, and effective microbicides to prevent human immunodeficiency virus HIV sexual transmission is needed. Unfortunately, most microbicides proved ineffective to prevent the risk of HIV-infection in clinical trials. We are working with G2-S16 polyanionic carbosilane dendrimer (PCD) as a new possible vaginal topical microbicide, based on its short reaction times, wide availability, high reproducibility, and quantitative yields of reaction. G2-S16 PCD exerts anti-HIV activity at an early stage of viral replication, by blocking gp120/CD4/CCR5 interaction, and providing a barrier against infection for long periods of time. G2-S16 PCD was stable at different pH values, as well as in the presence of seminal fluids. It maintained the anti-HIV activity against R5/X4 HIV over time, did not generate any type of drug resistance, and retained the anti-HIV effect when exposed to semen-enhanced viral infection. Importantly, G2-S16 PCD did not modify vaginal microbiota neither in vitro or in vivo. Histopathological examination did not show vaginal irritation, inflammation, lesions, or damage in the vaginal mucosa, after administration of G2-S16 PCD at different concentrations and times in female mice and rabbit animal models. Based on these promising data, G2-S16 PCD could become a good, safe, and readily available candidate to use as a topical vaginal microbicide against HIV.

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Updates in the management and future landscape of urothelial carcinoma

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220971026 ◽

2020 ◽

pp. 107815522097102

Author(s):

Kirollos S Hanna ◽

Maren Campbell ◽

Adam Kolling ◽

Alex Husak ◽

Sabrina Sturm ◽

...

Keyword(s):

Clinical Trials ◽

Urothelial Carcinoma ◽

Metastatic Disease ◽

Checkpoint Inhibitors ◽

Early Stage ◽

Locally Advanced ◽

The United States ◽

Cancer Type ◽

Antibody Drug Conjugate ◽

Early Stage Disease

Urothelial carcinoma is the sixth most common cancer type in the United States. Although most patients present with early stage disease which is associated with improved outcomes, many will progress to locally advanced or metastatic disease. Immune checkpoint inhibitors have significantly impacted the treatment paradigm for patients and have resulted in improved survival rates. Despite their proven efficacy, many ongoing clinical trials continue to refine combinations with chemotherapy, sequencing of therapies and the role of ligand expression. Additionally, novel targets have been identified for advanced urothelial carcinoma and have led to the approval of the antibody-drug conjugate, enfortumab vedotin, and the fibroblast growth factor receptor-targeted, erdafitinib. Enrollment in a clinical trial is strongly encouraged for all stages of advanced or metastatic disease. Numerous ongoing clinical trials are likely to impact the treatment armamentarium for patients. In this manuscript, we highlight key updates in the clinical management for patients and outline ongoing trials.

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Bispecific antibodies targeting dual tumor-associated antigens in cancer therapy

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-020-03404-6 ◽

2020 ◽

Vol 146 (12) ◽

pp. 3111-3122

Author(s):

Shuyu Huang ◽

Sander M. J. van Duijnhoven ◽

Alice J. A. M. Sijts ◽

Andrea van Elsas

Keyword(s):

Clinical Trials ◽

Cancer Therapy ◽

Clinical Evaluation ◽

Immune Cell ◽

Early Stage ◽

Relevant Literature ◽

Hematologic Malignancies ◽

Bispecific Antibodies ◽

Tumor Associated Antigens ◽

Tumor Selectivity

Abstract Purpose Bispecific antibodies (BsAbs) have emerged as a leading drug class for cancer therapy and are becoming increasingly of interest for therapeutic applications. As of April 2020, over 123 BsAbs are under clinical evaluation for use in oncology (including the two marketed BsAbs Blinatumomab and Catumaxomab). The majority (82 of 123) of BsAbs under clinical evaluation can be categorized as bispecific immune cell engager whereas a second less well-discussed subclass of BsAbs targets two tumor-associated antigens (TAAs). In this review, we summarize the clinical development of dual TAAs targeting BsAbs and provide an overview of critical considerations when designing dual TAA targeting BsAbs. Methods Herein the relevant literature and clinical trials published in English until April 1st 2020 were searched using PubMed and ClinicalTrials.gov database. BsAbs were considered to be active in clinic if their clinical trials were not terminated, withdrawn or completed before 2018 without reporting results. Data missed by searching ClinicalTrials.gov was manually curated. Results Dual TAAs targeting BsAbs offer several advantages including increased tumor selectivity, potential to concurrently modulate two functional pathways in the tumor cell and may yield improved payload delivery. Conclusions Dual TAAs targeting BsAbs represent a valuable class of biologics and early stage clinical studies have demonstrated promising anti-tumor efficacy in both hematologic malignancies and solid tumors.

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Revisiting the Amyloid Cascade Hypothesis: From Anti-Aβ Therapeutics to Auspicious New Ways for Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21165858 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5858 ◽

Cited By ~ 3

Author(s):

Md. Sahab Uddin ◽

Md. Tanvir Kabir ◽

Md. Sohanur Rahman ◽

Tapan Behl ◽

Philippe Jeandet ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Clinical Symptoms ◽

Neurodegenerative Disorder ◽

Early Stage ◽

Amyloid Β ◽

Aβ Oligomers ◽

Aβ Aggregation ◽

Clinical Benefits

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-β (Aβ), a peptide of 40–42 amino acids. The conversion of Aβ into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aβ accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aβ monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aβ and antagonize Aβ aggregation, or raise Aβ clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aβ which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aβ oligomers have exhibited exciting findings. Nevertheless, Aβ oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aβ monomer or Aβ plaques ought to have displayed valuable clinical benefits. In this article, Aβ-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.

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Knowledge-Based Strategies and Systems

Knowledge Management Strategies ◽

10.4018/978-1-59904-603-7.ch001 ◽

2011 ◽

pp. 1-62 ◽

Cited By ~ 1

Author(s):

Meir Russ ◽

J. Greg Jones ◽

Jeannette K Jones

Keyword(s):

Knowledge Management ◽

Life Cycle ◽

Early Stage ◽

Management Strategies ◽

Academic Research ◽

Business Strategies ◽

Knowledge Based Systems ◽

Academic Literature ◽

Knowledge Based ◽

New Research

Knowledge management strategies and implementation of knowledge-based systems have gained importance over the last decade. However, many organizations are not able to develop “winning” knowledge-based strategies and others waste signifi- cant monies when the knowledge-based systems they invest in fail to produce the desired results. To address the challenges faced by these organizations, a recently developed framework for strategic dilemmas was proposed by Russ, Jones, and Fineman (2006) to aid in the development of knowledge-based (KB) strategies. The framework (C3EEP) identifies six dilemmas that organizations should balance when considering their knowledge management and business strategies. Examples of such dilemmas include the balance between concealment (secrecy) vs. transparency, complementary vs. destroying, and the balance between exploitation and exploration. The framework compliments the six stages in the life cycle of KB systems (KBS) as identified by the academic literature that discusses the development and implementation of KBS from the information systems (IS) perspective (e.g., Lytras, Pouloudi, & Poulymenakou, 2002; Nissen, Kamel, & Sengupta, 2000). This interaction/ linkage between KB strategies and systems is crucial for the success of both. Academic research supports the complex relationship between the two. However, there is no conclusive formula for managing this relationship to achieve success. The purpose of this study will be to identify crossovers between the two streams (strategy and systems) of research by using a systematic literature review. For example, is the academic literature focusing mostly on the learning aspect (late stage in the life cycle) of the exploration strategy while largely ignoring the discussion about attracting the appropriate knowledge (early stage in the life cycle) for this kind of strategy? Or does the academic literature focus on populating a KBS with appropriate complementary knowledge while largely ignoring the dynamics of the transfer of destroying knowledge (learning aspect)? The authors hope to accomplish three goals in this study: (1) to continue the validation of the two (C3EEP and KBS life cycle) frameworks; (2) to identify new research opportunities; and (3) to focus managerial attention on areas of importance in KB strategies and systems that lack depth of academic discussion.

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