Fan and colleagues demonstrate that when erythropoietin connects with its receptor protein (EpoR), it launches a chain of events that activates Src, a crucial component of a pathway that trastuzumab blocks. It also shuts down a well-known tumor-suppressing gene called PTEN that is believed to be important to trastuzumab's activity against cancer cells.
There is controversy in academic circles about the role and function of EpoR in cancer cells and other types of cells not involved in blood production. It's important to note, Fan said, the team found no evidence that recombinant erythropoietin alone promotes cancer growth.
Tracking down the details
In three HER2-positive breast cancer cell lines, trastuzumab inhibited cell survival and proliferation, while recombinant erythropoietin stimulated cell survival and growth. When the three lines were treated together with trastuzumab and the anemia drug, cell survival increased from 58 percent to 80 percent, 57 percent to 77 percent, and 34 percent to 57.5 percent, respectively.
Two HER2-positive breast cancer cell types were introduced to mice, who then either received mock treatment, trastuzumab only, erythropoietin only or both drugs. Tumors treated with trastuzumab either shrank or stopped growing, with average tumor volume close to zero after 50 days in one cell line and barely registering in another. Growth of tumors treated with erythropoietin closely tracked the control group, increasing rapidly to an average volume of 1,500 cubic millimeters in one line and 600 mm3 in another. Tumors treated with both drugs grew more slowly to about 700 mm3 and 300 mm3.
Improved patient survival in small study
In a retrospective case-control study of patients with HER2-positive breast cancer that had spread, the team compared overall survival and pr
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center