Researchers at the Children’s Hospital in Boston have come up with a way to detect microscopic cancerous tumors in mice at a very early stage by using Ciphergen’s ProteinChip technology to measure the levels of certain proteins in platelets.
The news, which triggered a huge jump in Ciphergen stock, was presented this week at the American Society of Hematology’s annual meeting in San Diego. The findings are significant because platelet monitoring allowed researchers to identify the presence of tumors before the tumors were able to begin recruiting new blood vessels to feed themselves, and to grow.
The platelet angiogenic profile — a measurement of proteins in platelets that contribute to the development of new blood vessels — is a biomarker for tumor development, much like high cholesterol levels are biomarkers for heart disease, explained Judah Folkman, one of the lead authors of the study presented this week.
The study is in press to be published in an upcoming issue of the journal Blood.
“Ninety-nine out of 100 human tumors never become angiogenic, meaning they never learn how to recruit new blood vessels,” said Folkman. “When they do become angiogenic, they start to release angiogenic proteins, and those proteins are picked up by platelets in blood.”
Folkman and his research group, including co-principal author Giannoula Klement, used SELDI protein chips from Ciphergen to identify a number of angiogenic proteins, including VEGF, bFGF, PDGF, PF4, endostatin and tumstatin that are elevated in platelets in the presence of microscopic human tumors implanted into mice. The tumors are so tiny that they would be undetectable by other clinical means.
In response to news of Folkman’s research group’s results, shares of Ciphergen soared by 27 percent on Dec. 7 to $4.20 per share.
“We are delighted to see that our SELDI ProteinChip technology has enabled the discovery and quantifiable assay of biomarkers, which potentially may be used for early diagnosis of cancer, allowing for earlier treatment,” said William Rich, CEO of Ciphergen.
To treat angiogenic tumors before they begin to recruit blood vessels and grow, Folkman suggested using an angiogenesis inhibitor drug, such as doxycyline, endostatin, angiostatin, or thalidomide. He is currently conducting a study in mice to see what effect one of these drugs could have on the development of implanted microscopic human tumors.
If results in mice show that drugs that inhibit angiogenesis could stifle tumor development, then a human clinical trial may be started on patients that have had a tumor taken out in the past who are at high risk of developing new tumors, Folkman said.
“You won’t know where the tumor is, so you can’t treat with radiotherapy or surgery,” Folkman pointed out. “And you can’t treat with chemotherapy because it’s cytotoxic. But what you can do is treat the biomarker until it goes down.”
This is the first time that scientists have looked at angiogenic proteins specifically in platelets, Folkman said. The researchers knew that the angiogenic proteins had to be going to some component in blood, other than plasma, because they were being secreted by tumors but were not elevated in plasma. They got the idea to look at platelets because they knew that platelets are the component in blood that are responsible for regulating blood vessel formation.
“It’s been known that those angiogenic proteins are there in platelets, but it hasn’t been known that they change [in level] in response to the presence of a very small, microscopic tumor,” said Folkman.
Tiny, non-angiogenic tumors that have a cancer genome but are not growing are actually quite common in humans, Folkman said. In fact, 98 percent of the population has an early-stage tumor in their thyroid. But of those tumors, only one out of every 1,000 ever switches to become an angiogenic, growing tumor, he said.
In breast cancer, about one out of 100 early-stage tumors convert to being angiogenic tumors, he added.
The platelet angiogenic profile can detect a wide range of tumor types and tumor sizes, but it remains to be seen if it can detect all tumor types, the researchers said. The profile can be used to track a tumor throughout its development, beginning from an early, in situ, or unmetastasized cancer, to a clinically visible stage.
As a tumor develops after it is become angiogenic, angiogenic proteins such as VEGF may be found to be elevated in plasma, Folkman pointed out.
“By that time you can see it in plasma, the tumor is about to be diagnosed,” he said.
Treatment of angiogenesis through angiogenesis inhibitor drugs could be analogous to the treatment of cholesterol using Pfizer’s antihypercholesterolemia drug Lipitor, Folkman said.
“Instead of waiting for the patient to get a heart attack, you start treating the biomarkers,” he said. “In this case, you’d be treating an invisible tumor guided by a biomarker which is the platelet angiogenic profile.”
An example of a good target for platelet angiogenic profile monitoring is someone who has had an operation to remove colon cancer, Folkman said. That individual could have a blood test taken every few months in addition to having x-rays periodically to see if a new tumor has developed.
“If the platelet angiogenic profile keeps rising over the years, it could mean that there is a metastasis hidden somewhere,” said Folkman.