A midnight discovery
Minerva stumbles upon cancer therapy breakthrough
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BOSTON— Nanotechnology, cancer and stem cell development company Minerva Biotechnology announced last month it has made significant discoveries that explain how a key molecular mechanism is involved in cancer cell growth and metastasis.
Using its proprietary nanoparticle technology, Minerva found antibody-based and small molecule therapeutics that disable MUC1, a cell surface receptor, and block cancer cell growth. The discovery may lead to better tumor development diagnostics and prognostics, according to Dr. Cynthia Bamdad, founder and CSO of Waltham, Mass.-based Minerva.
And it happened completely by accident, Bamdad says.
"About eight years ago, we set out to show the usefulness of our nanoparticles and how they could be used to show different protein interactions," she says. "We saw on one of controls that one of the proteins we were looking at was this little small part of the MUC1 protein, called MUC1* (star). When MUC1* is cleaved, the cleaved part comes down and becomes a ligand for the receptors. We thought, 'hmm, this is kind of a sexy topic.'"
According to scientific literature, MUC1 is aberrantly expressed on 75 percent of all human solid tumors, 96 percent of breast cancers and 47 percent of prostate cancers, as well as high percentages of ovarian, colorectal, non-small cell lung and pancreatic cancers. Circulating MUC1 is currently used as a diagnostic marker for breast cancer and over expression also has been shown by many studies to be correlated with poor clinical outcome.
Minerva found that MUC1* is expressed to much higher levels than MUC1 in a variety of human tumor tissues. The company discovered that once cleaved, MUC1* dimerizes with itself and other growth factor receptors through binding of a newly discovered ligand for MUC1*, called NM23.
Binding and dimerization then activates the tumor to unregulated cell growth, invasion and metastasis. Blocking MUC1* dimerization and NM23 binding leads to cancer cell death, Minerva found.
"It was two o'clock in the morning when we found out how it works, and it was a real boo-hoo moment," Bamdad says. "For 25 years, everyone has known MUC1 should be a good candidate for cancer therapeutics because it has an aberrant expression of MUC1 in the cancers that pose the biggest problems for both men and women. But we found the part that is really operative in cancers is this tiny MUC1*, which should be the drug target."
For the next eight years, Minerva used its nanoparticle technology to find compounds that disable the MUC1 portion of the protein while not affecting the MUC1 protein on normal cells. Minerva will continue to research the potential of MUC1* and will next examine drug resistance and up-regulation of MUC1* in women with breast cancer.
Minerva also will develop potential cancer therapy targets through early FDA approval and may seek a joint venture agreement with a pharmaceutical company to complete development, Bamdad says.
"I think the industry is moving away from agents that kill cells and toward targeted therapeutics," she says. "The goal is to kill more cancer cells than your healthy cells. The end story is that this is good news for us because our small molecules and antibodies don't bind to MUC1." DDN
Using its proprietary nanoparticle technology, Minerva found antibody-based and small molecule therapeutics that disable MUC1, a cell surface receptor, and block cancer cell growth. The discovery may lead to better tumor development diagnostics and prognostics, according to Dr. Cynthia Bamdad, founder and CSO of Waltham, Mass.-based Minerva.
And it happened completely by accident, Bamdad says.
"About eight years ago, we set out to show the usefulness of our nanoparticles and how they could be used to show different protein interactions," she says. "We saw on one of controls that one of the proteins we were looking at was this little small part of the MUC1 protein, called MUC1* (star). When MUC1* is cleaved, the cleaved part comes down and becomes a ligand for the receptors. We thought, 'hmm, this is kind of a sexy topic.'"
According to scientific literature, MUC1 is aberrantly expressed on 75 percent of all human solid tumors, 96 percent of breast cancers and 47 percent of prostate cancers, as well as high percentages of ovarian, colorectal, non-small cell lung and pancreatic cancers. Circulating MUC1 is currently used as a diagnostic marker for breast cancer and over expression also has been shown by many studies to be correlated with poor clinical outcome.
Minerva found that MUC1* is expressed to much higher levels than MUC1 in a variety of human tumor tissues. The company discovered that once cleaved, MUC1* dimerizes with itself and other growth factor receptors through binding of a newly discovered ligand for MUC1*, called NM23.
Binding and dimerization then activates the tumor to unregulated cell growth, invasion and metastasis. Blocking MUC1* dimerization and NM23 binding leads to cancer cell death, Minerva found.
"It was two o'clock in the morning when we found out how it works, and it was a real boo-hoo moment," Bamdad says. "For 25 years, everyone has known MUC1 should be a good candidate for cancer therapeutics because it has an aberrant expression of MUC1 in the cancers that pose the biggest problems for both men and women. But we found the part that is really operative in cancers is this tiny MUC1*, which should be the drug target."
For the next eight years, Minerva used its nanoparticle technology to find compounds that disable the MUC1 portion of the protein while not affecting the MUC1 protein on normal cells. Minerva will continue to research the potential of MUC1* and will next examine drug resistance and up-regulation of MUC1* in women with breast cancer.
Minerva also will develop potential cancer therapy targets through early FDA approval and may seek a joint venture agreement with a pharmaceutical company to complete development, Bamdad says.
"I think the industry is moving away from agents that kill cells and toward targeted therapeutics," she says. "The goal is to kill more cancer cells than your healthy cells. The end story is that this is good news for us because our small molecules and antibodies don't bind to MUC1." DDN
