scholarly journals Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection

2021 ◽  
Author(s):  
Marcello Allegretti ◽  
Maria Candida Cesta ◽  
Mara Zippoli ◽  
Andrea Beccari ◽  
Carmine Talarico ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Estrogen Receptor ◽  
Early Stage ◽  
Clinical Development ◽  
Immune Memory ◽  
Therapeutic Drug ◽  
The Novel ◽  
Drug Candidates ◽  
Receptor Modulator ◽  
Attractive Candidate

AbstractThe ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates strategies to identify prophylactic and therapeutic drug candidates to enter rapid clinical development. This is particularly true, given the uncertainty about the endurance of the immune memory induced by both previous infections or vaccines, and given the fact that the eradication of SARS-CoV-2 might be challenging to reach, given the attack rate of the virus, which would require unusually high protection by a vaccine. Here, we show how raloxifene, a selective estrogen receptor modulator with anti-inflammatory and antiviral properties, emerges as an attractive candidate entering clinical trials to test its efficacy in early-stage treatment COVID-19 patients.

scholarly journals WEE1 Inhibitor: Clinical Development

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Anthony Kong ◽  
Hisham Mehanna
Keyword(s):  
Clinical Trials ◽  
Tp53 Mutation ◽  
Predictive Biomarker ◽  
Concurrent Chemotherapy ◽  
Clinical Development ◽  
Novel Agents ◽  
The Novel ◽  
Grade 3 ◽  
Chemotherapy Agents

Abstract Purpose of Review WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents. Recent Findings Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. Summary There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.

Hormonal Therapy for the Treatment of Postmenopausal Breast Cancer Patients

2008 ◽  
Vol 21 (1) ◽  
pp. 36-45
Author(s):  
Rebecca E. Greene ◽  
Vivian Tsang
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Postmenopausal Women ◽  
Hormonal Therapy ◽  
Early Stage ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Receptor Modulator

Breast cancer is the most common cancer diagnosed and the second leading cause of cancer-related death in women. The majority of breast cancers diagnosed in postmenopausal women are hormone receptor positive and involve therapy with hormonal agents. Tamoxifen, a selective estrogen-receptor modulator, has been the mainstay of hormonal therapy since the 1970s. The more recent approval and success of aromatase inhibitors, such as anastrozole, letrozole, and exemestane, have seen these agents move to the front line of therapy for postmenopausal women with hormone-positive breast cancer in the adjuvant and metastatic settings. Fulvestrant, a selective estrogen receptor— downregulator, provides an additional hormonal therapy with a novel mechanism of action. This article reviews the current literature available regarding the use of these agents for postmenopausal women with early stage or advanced breast cancer.

scholarly journals SERMs in the prevention and treatment of postmenopausal osteoporosis: an update

2010 ◽  
Vol 54 (2) ◽  
pp. 200-205 ◽  
Author(s):  
Jaime Kulak Júnior ◽  
Carolina Aguiar Moreira Kulak ◽  
Hugh S. Taylor
Keyword(s):  
Estrogen Receptor ◽  
Postmenopausal Osteoporosis ◽  
Single Agent ◽  
Clinical Development ◽  
Target Tissue ◽  
New Approach ◽  
Estrogen Receptor Modulators ◽  
Receptor Modulator ◽  
Prevention And Treatment ◽  
Receptor Modulators

Selective estrogen receptor modulators (SERMs) have the ability to bind the estrogen receptor (ER) and are known to confer ER agonist or antagonist effects depending on the target tissue. A number of newer SERMs, including bazedoxifene, lasofoxifene and ospemifene, are currently under clinical development for the prevention and treatment of postmenopausal osteoporosis and for other indications. Although the possibility of developing a single agent that has all of the desired characteristics of an ideal SERM seems to be unlikely, progress in the clinical development of SERMs targeted to the ER suggests that these newer compounds may have attributes that represent an improvement relative to existing SERMs. A new approach to menopausal therapy is the tissue selective estrogen complex or the pairing of a selective estrogen receptor modulator with estrogens. Further investigation will help to clarify relative benefits/risks of novel SERMs in development within specific indications.

scholarly journals The future of anti-CD20 monoclonal antibodies: are we making progress?

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 2993-3001 ◽  
Author(s):  
Waleed Alduaij ◽  
Tim M. Illidge
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Personalized Medicine ◽  
Clinical Development ◽  
The Novel ◽  
Next Generation ◽  
B Cell Malignancies ◽  
Clinical Community ◽  
Anti Cd20

AbstractThe anti-CD20 monoclonal antibody (mAb) rituximab has revolutionized the treatment of B-cell malignancies. This unprecedented success has not only substantially changed the mindset of the clinical community about the ability of mAb to improve outcomes but has catalyzed the interest in the pharmaceutical industry to develop the next generation of anti-CD20 mAbs. Since the introduction of rituximab 15 years ago, we have learned much about the potential mechanisms underlying the therapeutic efficacy of anti-CD20 mAbs. In parallel, many novel anti-CD20 mAbs have entered the clinic, each designed with modifications to structure aimed at further improving efficacy. On review of the newer generation of anti-CD20 mAbs entering clinical trials, it appears that the link between the novel mechanistic insights and the development of these next-generation anti-CD20 mAbs is unclear. As we move into an era of personalized medicine, it will become increasingly important for us to develop closer links between the emerging mechanistic insights and the clinical development, to further enhance the potency of anti-CD20 mAbs beyond that achieved with rituximab.

scholarly journals Anastrozole Use in Early Stage Breast Cancer of Post-Menopausal Women

2009 ◽  
Vol 1 ◽  
pp. CMT.S9 ◽  
Author(s):  
Monica Milani ◽  
Gautam Jha ◽  
David A. Potter
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Estrogen Receptor ◽  
Hormone Receptor ◽  
Early Stage ◽  
Breast Cancers ◽  
Adjuvant Setting ◽  
Hormone Receptor Positive ◽  
Menopausal Women ◽  
Post Menopausal

The majority of breast cancers express the estrogen receptor and depend on estradiol (E2) for their growth. Hormonal therapy aims at depriving estrogen signaling either by using selective estrogen receptor modulators (SERM)–-that interfere with the binding of E2 to its receptor (ER)–-or aromatase inhibitors (AI)–-that block the aromatase-dependent synthesis of E2. While SERMs are recommended for both pre- and post-menopausal patients, AIs are indicated only for post-menopausal patients. For the past 20 years, the SERM tamoxifen has been considered the “gold standard” for the treatment of hormone receptor positive breast cancers. However, tamoxifen's role is now challenged by third generation AIs, such as anastrozole, which exhibit greater efficacy in the adjuvant setting in several recently reported trials. This review will focus on anastrozole's mechanism of action, dosing, pharmacology, pharmacokinetics, and clinical applications. It will briefly discuss the clinical trials that determined anastrozole's efficacy in the treatment of advanced breast cancer (ABC) and in the neo-adjuvant setting. Finally, it will present the clinical trials that established anastrozole as a frontline agent in the treatment of post-menopausal women with hormone receptor positive early breast cancer.

Oral drug repositioning candidates and synergistic remdesivir combinations for the prophylaxis and treatment of COVID-19

2020 ◽  
Author(s):  
Malina A. Bakowski ◽  
Nathan Beutler ◽  
Emily Chen ◽  
Tu-Trinh H. Nguyen ◽  
Melanie G. Kirkpatrick ◽  
...  
Keyword(s):  
Drug Repositioning ◽  
Drug Repurposing ◽  
Oral Drug ◽  
Therapeutic Drug ◽  
The Novel ◽  
High Content Imaging ◽  
Drug Candidates ◽  
Polymerase Inhibitor ◽  
Approved Drugs

AbstractThe ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. A high-throughput, high-content imaging assay of human HeLa cells expressing the SARS-CoV-2 receptor ACE2 was used to screen ReFRAME, a best-in-class drug repurposing library. From nearly 12,000 compounds, we identified 66 compounds capable of selectively inhibiting SARS-CoV-2 replication in human cells. Twenty-four of these drugs show additive activity in combination with the RNA-dependent RNA polymerase inhibitor remdesivir and may afford increased in vivo efficacy. We also identified synergistic interaction of the nucleoside analog riboprine and a folate antagonist 10-deazaaminopterin with remdesivir. Overall, seven clinically approved drugs (halofantrine, amiodarone, nelfinavir, simeprevir, manidipine, ozanimod, osimertinib) and 19 compounds in other stages of development may have the potential to be repurposed as SARS-CoV-2 oral therapeutics based on their potency, pharmacokinetic and human safety profiles.

scholarly journals Remote Cardiac Safety Monitoring through the Lens of the FDA Biomarker Qualification Evidentiary Criteria Framework: A Case Study Analysis

2021 ◽  
Vol 5 (1) ◽  
pp. 103-113
Author(s):  
Elena S. Izmailova ◽  
William A. Wood ◽  
Qi Liu ◽  
Vadim Zipunnikov ◽  
Daniel Bloomfield ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Data Collection ◽  
Early Stage ◽  
Contextual Information ◽  
Data Interpretation ◽  
Medical Product ◽  
Cardiac Monitoring ◽  
Clinical Safety ◽  
Drug Candidates

Clinical safety findings remain one of the reasons for attrition of drug candidates during clinical development. Cardiovascular liabilities are not consistently detected in early-stage clinical trials and often become apparent when drugs are administered chronically for extended periods of time. Vital sign data collection outside of the clinic offers an opportunity for deeper physiological characterization of drug candidates and earlier safety signal detection. A working group representing expertise from biopharmaceutical and technology sectors, US Food and Drug Administration (FDA) public-private partnerships, academia, and regulators discussed and presented a remote cardiac monitoring case study at the FNIH Biomarkers Consortium Remote Digital Monitoring for Medical Product Development workshop to examine applicability of the biomarker qualification evidentiary framework by the FDA. This use case examined the components of the framework, including the statement of need, the context of use, the state of the evidence, and the benefit/risk profile. Examination of results from 2 clinical trials deploying 510(k)-cleared devices for remote cardiac data collection demonstrated the need for analytical and clinical validity irrespectively of the regulatory status of a device of interest, emphasizing the importance of data collection method assessment in the context of intended use. Additionally, collection of large amounts of ambulatory data also highlighted the need for new statistical methods and contextual information to enable data interpretation. A wider adoption of this approach for drug development purposes will require collaborations across industry, academia, and regulatory agencies to establish methodologies and supportive data sets to enable data interpretation and decision-making.

Sign in / Sign up

Export Citation Format

Share Document