| Title |
Development of venetoclax for therapy of lymphoid malignancies
|
|---|---|
| Published in |
Drug Design, Development and Therapy, March 2017
|
| DOI | 10.2147/dddt.s109325 |
| Pubmed ID | |
| Authors |
Huayuan Zhu, Alexandru Almasan |
| Abstract |
B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients. Also, unlike the other targeted agents, it is effective against tumor cells that reside in the blood marrow. Despite its promising outcome in CLL, preclinical data have already uncovered mechanistic insights underlying venetoclax resistance, such as upregulation of MCL-1 or BCL-xL expression and protective signaling from the microenvironment. In this review, we describe the role of the BCL-2 family in the pathogenesis of B-cell lymphoid malignancies, the development of venetoclax, and its current clinical outcome in CLL and other B-cell malignancies. We also discuss the resistance mechanisms that develop following venetoclax therapy, potential strategies to overcome them, and how this knowledge can be translated into clinical applications. |
Mendeley readers
The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 63 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 13 | 21% |
| Student > Master | 8 | 13% |
| Student > Postgraduate | 5 | 8% |
| Student > Bachelor | 5 | 8% |
| Student > Doctoral Student | 3 | 5% |
| Other | 6 | 10% |
| Unknown | 23 | 37% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 11 | 17% |
| Agricultural and Biological Sciences | 8 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 10% |
| Medicine and Dentistry | 6 | 10% |
| Immunology and Microbiology | 3 | 5% |
| Other | 6 | 10% |
| Unknown | 23 | 37% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 November 2022.
All research outputs
#3,416,577
of 25,382,440 outputs
Outputs from Drug Design, Development and Therapy
#200
of 2,268 outputs
Outputs of similar age
#60,442
of 324,443 outputs
Outputs of similar age from Drug Design, Development and Therapy
#6
of 50 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,268 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has done particularly well, scoring higher than 90% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 324,443 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 50 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.