ABT-510
Encyclopedia
ABT-510 is a molecular therapeutic drug used to treat cancer. According to the Journal of Clinical Oncology, ABT-510 is a "subcutaneously (SC) administered nonapeptide thrombospondin analogue in phase 2 clinical development for treatment of advanced malignancies."
ABT-510 is a new Abbott Laboratories
compound showing promise as an angiogenesis inhibitor
or anti-angiogenic agent, meaning it works by stopping the growth of new blood vessels. This Thrombospondin 1
mimetic works through CD36
and has been shown to block angiogenesis in vitro and in vivo and to slow tumor growth in mice.
ABT-510 was shown to be effective in both xenograft models and in a study of companion dogs with spontaneous tumors. Not only were objective responses observed after 60 days, but a decrease in levels of circulating endothelial cells was also found .
In human studies, ABT-510 was found to be safe and have efficacy in phase I trials in combination regimens
, and as a single agent, where its use was associated with a decrease in bFGF levels and stable disease in six patients for at least six months .
The combination of bevacizumab
and ABT-510 has been shown (in a phase I study) to be effective in promoting stable disease in 44% of patients with advanced solid tumors .
Unfortunately, the recent phase II study of ABT-510 for treatment of metastatic melanoma
failed to reach its primary endpoint
resulting in early termination of the study. Only three out of twenty-one patients reached the primary endpoint of progression-free survival at 18 weeks, but these three patients remained progression-free for 21, 34, and 42 weeks. However, biomarker data collected during this study showed a decrease in VEGF-C, circulating endothelial cells, and CD146
and CD34/133 counts, and a maximum tolerated dose has still not been established. Further study could consider a higher dose and/or combination treatment .
ABT-510 is a new Abbott Laboratories
Abbott Laboratories
Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
compound showing promise as an angiogenesis inhibitor
Angiogenesis inhibitor
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels . Some angiogenesis inhibitors are a normal part of the body's control, some are administered as drugs, and some come from diet....
or anti-angiogenic agent, meaning it works by stopping the growth of new blood vessels. This Thrombospondin 1
Thrombospondin 1
Thrombospondin 1, also known as THBS1, is a protein that in humans in encoded by the THBS1 gene.Thrombospondin 1 is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to...
mimetic works through CD36
CD36
CD36 is an integral membrane protein found on the surface of many cell types in vertebrate animals and is also known as FAT, SCARB3, GP88, glycoprotein IV and glycoprotein IIIb . CD36 is a member of the class B scavenger receptor family of cell surface proteins...
and has been shown to block angiogenesis in vitro and in vivo and to slow tumor growth in mice.
ABT-510 was shown to be effective in both xenograft models and in a study of companion dogs with spontaneous tumors. Not only were objective responses observed after 60 days, but a decrease in levels of circulating endothelial cells was also found .
In human studies, ABT-510 was found to be safe and have efficacy in phase I trials in combination regimens
, and as a single agent, where its use was associated with a decrease in bFGF levels and stable disease in six patients for at least six months .
The combination of bevacizumab
Bevacizumab
Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....
and ABT-510 has been shown (in a phase I study) to be effective in promoting stable disease in 44% of patients with advanced solid tumors .
Unfortunately, the recent phase II study of ABT-510 for treatment of metastatic melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
failed to reach its primary endpoint
Clinical endpoint
In a clinical research trial, a clinical endpoint generally refers to occurrence of a disease, symptom, sign or laboratory abnormality that constitutes one of the target outcomes of the trial, but may also refer to any such disease or sign that strongly motivates the withdrawal of that individual...
resulting in early termination of the study. Only three out of twenty-one patients reached the primary endpoint of progression-free survival at 18 weeks, but these three patients remained progression-free for 21, 34, and 42 weeks. However, biomarker data collected during this study showed a decrease in VEGF-C, circulating endothelial cells, and CD146
CD146
CD146 also known as the melanoma cell adhesion molecule or cell surface glycoprotein MUC18, is a 113kDa cell adhesion molecule currently used as a marker for endothelial cell lineage...
and CD34/133 counts, and a maximum tolerated dose has still not been established. Further study could consider a higher dose and/or combination treatment .