BOSTON — A new protein that can serve as both a drug target and a diagnostic biomarker for breast cancer was presented here this week at the Biomarker Pipeline conference.
The new protein, called GP88, was developed by the 5-year-old Columbia, Md.-based company A&G Pharmaceutical.
“From the beginning it was my intention to identify a target that had both diagnostic and therapeutic potential,” Ginette Serrero, the president and chief scientific officer of the company, told ProteoMonitor. “That was not an accident.”
A number of scientists at the conference addressed the importance of having “companion diagnostics” to accompany the drug-development process (see theranostics story). In theory, the companion can help drug makers in selecting patient populations for their clinical trials, and aid physicians in prescribing certain medicines and in tracking treatment progression.
The advantage of having a molecule with both therapeutic and diagnostic properties is that the molecule, in theory, can more easily be pushed out into the market as a package deal with coordinated timelines.
During her talk, Serrero presented published experimental data showing that GP88 secretion increases with increased tumorigenicity in human breast cancer cells. She also showed that if GP88 production is inhibited in mice through the use of GP88 anti-sense RNA, then breast cancer cell growth is inhibited.
Furthermore, Serrero presented published data showing that in the case of breast cancer cells that are resistant to the cancer drug tamoxifen, the resistant cells overexpress GP88. If GP88 production is inhibited in the resistant cells, then tamoxifen responsiveness is restored.
Serrero said her company is currently looking to develop a breast cancer therapeutic based upon a monoclonal antibody to GP88.
“We are looking to partner with somebody in developing the therapeutic,” said Serrero.
On the diagnostic side, a GP88 biopsy staining kit serves as a good indicator as to whether a tissue is benign or cancerous, and what grade of tumorigenicity the tissue is, Serrero said. According to her data, 96 percent of benign biopsies showed negative staining for GP88, while 67 percent of non-invasive ductal carcinoma biopsies stained positive for GP88, and 80 percent of invasive ductal carcinoma biopsies stained positive for GP88.
Serrero’s company has also developed a kit for monitoring the levels of GP88 in serum. According to Serrero’s data, serum levels of GP88 are elevated in patients who have breast cancer recurrence.
“I think definitely that this is apparently convincing. I believe that it’s really promising,” said Albert Li, president and CEO of Advanced Pharmaceutical Sciences, a Baltimore-based company that focuses on early evaluation of drug efficacy, metabolism, and toxicity. “The need now is for further validation with more samples to find out what is the false positive and false negative rate, as well as some rigorous testing comparing the [GP88 diagnostic] kit with PCR and western blotting.”
Li suggested that Serrero’s company should foster an open collaboration with centers with lots of breast cancer patients in doing the initial validation to test the performance of the diagnostic kits.
Serrero said her company is planning on filing this year for FDA approval of the diagnostic tests.
In getting the GP88-based diagnostic on the market, the biggest challenge will be getting the right clinical samples so that researchers can perform a retrospective clinical study, Serrero said.
“A retrospective study is much faster, in terms of going for FDA approval,” Serrero said. “But if we don’t get the right samples, we may have to do a prospective study, and that would take much longer, and a lot more money.”
Currently, the HER2 test and the estrogen receptor test are the standard biomarker tests used for helping physicians determine which treatment regimen to administer for breast cancer. Patients who overexpress HER2 and patients who test positive in the estrogen receptor test may be less responsive to standard breast cancer therapies, including chemotherapy.
If a patient tests positive for HER2, she may be treated with Herceptin to first lower levels of HER2, then treated with standard therapies such as chemotherapy or radiation. Similarly, if a patient tests positive in the estrogen receptor test, she may be first treated with the drug tamoxifen before undergoing standard treatments.
In comparison with HER2, GP88 has a broader reach, Serrero said. While only about 25 percent of breast cancer patients test positive for overexpression of HER2, about 80 percent of breast cancer patients test positive for overexpression of GP88.
Serrero said that ultimately, she hopes that the GP88 diagnostic kits can be used to further help physicians determine what treatment regimen to administer for breast cancer patients.
Based on data linking GP88 overproduction to tamoxifen resistance, Serrero predicted that a good start to a treatment decision tree would be to test breast cancer patients with the GP88 test, in addition to the HER2 and estrogen receptor tests. If a woman tests positive for the GP88 test, then physicians may want to reconsider administering tamoxifen, Serrero suggested, and consider treating with an anti-GP88 therapeutic.
It is too early to tell what treatment combination would be best, but the GP88 diagnostic and an anti-GP88 therapeutic would provide useful additional information and treatment options, Serrero said.