Breast Cancer Clinical Trial
Official title:
Autotaxin (ATX) as a Marker for Breast Cancer
Breast cancer is the leading cause of cancer death in women worldwide. According to the GLOBOCAN 2018 worldwide estimates of cancer incidence and mortality, in 2018, about 2,088,849 new cases were diagnosed and approximately 626,679 women were predicted to die from the disease . It is the leading cause of cancer related mortality, representing15% of deaths per year worldwide .
Breast cancer is the most common malignancy in females in Egypt. It accounts for 32 % of
cancer in women . Breast cancer in Egypt carries an unfavorable prognosis with 29% mortality
and 3.7:1 incidence to mortality ratio .
Despite the rising incidence of breast cancer, the survival rates have improved in recent
years due to the deep research in biological behavior of breast cancer . Although the current
5-year survival for primary breast cancer is relatively high (ranging from 80% to 92% in
different populations) survival rates decrease to less than 25% when the disease becomes
metastatic .These data support the need to develop more efficient strategies for preventive,
intervention, evaluation of therapy, and prediction of prognosis .
Autotaxin (ATX) is a glycoprotein encoded by the ENPP2 (Ectonucleotide
Pyrophosphatase/Phosphodiesterase 2) gene located on chromosome 8. Identical to
lysophospholipase D, ATX plays a role in the synthesis of the bioactive lipid mediator
lysophosphatidate (LPA) from lysophosphatidylcholine (LPC) .
LPA acts through specific G protein-coupled receptors (GPCRs) to promote cellular
proliferation, migration, and survival . ATX expression was also reported higher in poorly
differentiated tumors and, in independent studies, is correlated with invasiveness of cancer
cells suggesting a higher metastatic potential of ATX-expressing tumors . ATX is generated
from platelets, endothelial cells, fibroblasts, and adipocytes and specifically, ATX from
adipocytes has an impact on plasma LPA level . Thus, adipocytes could be an important origin
of ATX in tumors. Breast cancer is a human cancer that has adipocyte-rich stroma. Adipose
tissue comprises 56% of non-lactating breast tissue, and 35% of lactating breast tissue .
ATX-LPA signaling has been reported to be involved in angiogenesis, tumor cell invasion, and
migration in breast cancer .
Increased ATX expression has also been reported in various forms of cancer, such as
glioblastoma, hepatocellular and thyroid carcinomas, pancreatic and hematological cancers. A
large number of evidence indicate that ATX-LPA is associated with chemotherapy resistance of
cancer, and in breast cancer, ATX can reverse cell apoptosis.
In a mouse model, α-bromomethylene phosphonate LPA (BrP-LPA), a dual ATX and pan-LPAR(
Lysophosphatidic acid receptor ) inhibitor, inhibited migration and invasion of breast cancer
cell lines and suppressed primary tumor and angiogenesis in a mouse xenograft study . Since
tumor and stromal cells in breast cancer express ATX-LPA signaling-related proteins,
inhibition of the ATX-LPA axis could be of therapeutic importance .Therefore, further study
ATX as a tumor marker in breast cancer is required.
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