scholarly journals Outsmarting the Virus

2021 ◽  
Vol 6 (3) ◽  
Author(s):  
John Hewitt

Variants in the SARS-CoV-2 virus control infectivity, severity, and immunity. Against this hydra, the best modes of defense are multipronged. John Hewitt takes stock of currently available SARS-CoV-2 therapies; in particular, he notes new combination therapies that strike at the heart of the virus to complement vaccinations and provide a defense the virus cannot outsmart.

2019 ◽  
Author(s):  
Mitchell G Lawrence ◽  
Laura H Porter ◽  
Daisuke Obinata ◽  
Shahneen Sandhu ◽  
Luke A Selth ◽  
...  

2018 ◽  
Author(s):  
Miriam Molina-Arcas ◽  
Christopher Moore ◽  
Sareena Rana ◽  
Febe van Maldegem ◽  
Stuart Horswell ◽  
...  

2018 ◽  
Author(s):  
M Molina-Arcas ◽  
C Moore ◽  
S Rana ◽  
F Van Maldegem ◽  
S Horswell ◽  
...  

2019 ◽  
Vol 10 (42) ◽  
pp. 9663-9672 ◽  
Author(s):  
Hongyu Li ◽  
Hennie Valkenier ◽  
Abigail G. Thorne ◽  
Christopher M. Dias ◽  
James A. Cooper ◽  
...  

Synthetic anion transporters are active in cystic fibrosis cells, and are additive to clinically-approved drugs, suggesting new combination therapies for this lethal genetic condition.


2019 ◽  
Vol 15 (2) ◽  
pp. 110-119
Author(s):  
Emilio Francesco Giunta ◽  
Giuseppe Argenziano ◽  
Gabriella Brancaccio ◽  
Erika Martinelli ◽  
Fortunato Ciardiello ◽  
...  

: Metastatic melanoma treatment has dramatically changed in the last few years, having a breakthrough with the introduction of targeted agents and immunotherapy. PD-1/PD-L1 pathway is one of the physiologic mechanisms of peripheral immune tolerance, but it also represents a mechanism of tumor immune escape. PD-1/PD-L1 inhibitors represent new immune-checkpoint drugs currently used in metastatic melanoma treatment. : Resistance to PD-1/PD-L1 axis blockade, which is the main cause of therapeutic failure during therapeutic use of these drugs, could be linked to several mechanism of immune escape. In fact, other inhibitory receptor such as CTLA-4, LAG-3, TIM-3 and TIGIT might be co-expressed on T cells, deleting the effect of anti-PD-1/PD-L1; overexpression of the enzyme IDO could cause immunosuppression through the depletion of tryptophan in the tumor microenvironment; defective c ostimulation (through reduced activity of 4-1BB and OX40 receptors) could result in T-cell energy. : Combination of anti-PD-1/PD-L1 with drugs targeting inhibitory or costimulatory receptors, intracellular pathways, enzymes or neoangiogenesis could be a possible strategy to overcome resistance to single PD-1/PD-L1 blockade. Clinical trials evaluating combination therapies have already showed interesting results, although most of them are still on going.


2018 ◽  
Vol 19 (8) ◽  
pp. 2453 ◽  
Author(s):  
Fabiana Conciatori ◽  
Chiara Bazzichetto ◽  
Italia Falcone ◽  
Sara Pilotto ◽  
Emilio Bria ◽  
...  

The mammalian target of rapamycin (mTOR) pathway regulates major processes by integrating a variety of exogenous cues, including diverse environmental inputs in the tumor microenvironment (TME). In recent years, it has been well recognized that cancer cells co-exist and co-evolve with their TME, which is often involved in drug resistance. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both the tumor immunity and angiogenesis. The activation of mTOR signaling is associated with these pro-oncogenic cellular processes, making mTOR a promising target for new combination therapies. This review highlights the role of mTOR signaling in the characterization and the activity of the TME’s elements and their implications in cancer immunotherapy.


2001 ◽  
Vol 34 ◽  
pp. 143 ◽  
Author(s):  
A.M. Di Bisceglie ◽  
D.E. Bernstein ◽  
V.R. Rustgi ◽  
N. Gitlin ◽  
L.J. Jeffers ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1336
Author(s):  
Moritz Fürstenau ◽  
Barbara Eichhorst

The approval of Bruton’s tyrosine kinase (BTK) inhibitors such as ibrutinib and acalabrutinib and the Bcl-2 inhibitor venetoclax have revolutionized the treatment of chronic lymphocytic leukemia (CLL). While these novel agents alone or in combination induce long lasting and deep remissions in most patients with CLL, their use may be associated with the development of clinical resistance. In this review, we elucidate the genetic basis of acquired resistance to BTK and Bcl-2 inhibition and present evidence on resistance mechanisms that are not linked to single genomic alterations affecting these target proteins. Strategies to prevent resistance to novel agents are discussed in this review with a special focus on new combination therapies.


Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 24
Author(s):  
Nikhita Kathuria-Prakash ◽  
Claire Drolen ◽  
Christopher A. Hannigan ◽  
Alexandra Drakaki

Introduction: Renal cell carcinomas (RCC) have been treated with immunotherapy for decades; the use of immune checkpoint inhibitors represents the most recent advance. In this review, we compare these new RCC immunotherapies, with a focus on achieving durable complete responses (CR). Review: Sorafenib and sunitinib were the first Food and Drug Administration (FDA)-approved targeted agents for RCC, with sunitinib eventually becoming the standard-of-care agent against which novel therapies are compared. In the last five years, many combination therapies based on the use of immune checkpoint inhibitors (ICIs) and receptor tyrosine kinase inhibitors (TKIs), including ipilimumab/nivolumab, nivolumab/cabozantinib, avelumab/axitinib, pembrolizumab/axitinib, and pembrolizumab/lenvatinib, have demonstrated superior overall survival (OS) and progression-free survival (PFS) compared to sunitinib. Ongoing clinical trials of hypoxia-induced factor-2 alpha (HIF-2a) inhibitors, chimeric antigen receptor T cell (CAR-T) therapy targeting CD70, and other new combination therapies have also shown promise and are currently under investigation. Conclusions: Many new combination therapies are approved for RCC treatment, and CR rates suggest that, in the era of immunotherapy, it may be possible to achieve durable responses and survival benefit in patients with metastatic RCC.


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