epidermal growth factor receptors

Nanoparticles Are Moving Us Toward a Cancer-Free World

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IN BRIEF
  • A new nanoparticle therapy that uses a minute gel pellet to deliver siRNA to cancer cells has reduced or eliminated carcinomas in in vivo tests in four mice.
  • The treatment is still in its very early stages, but joins a growing number of nanoparticle therapies looking to improve how we combat disease on a cellular level.

LOWERING DEFENSES

While some medical studies focus on developing completely new medicines and treatments for diseases, others attempt to improve existing options. In an attempt at the latter, researchers from the Georgia Institute of Technology have developed a new nanoparticle-based treatment that makes chemotherapy more effective.

Their treatment targets epidermal growth factor receptors (EGFRs). These cell structures are found in epithelial cells, which line the body’s organs. In a healthy cell, they jumpstart a variety of typical cellular functions, but in cancer cells, they are overproduced. “The problem is that because of this overexpression, many cellular functions, including cell replication and resistance to certain chemotherapy drugs, are dramatically cranked up,” says chief researcher John McDonald.

When its DNA is damaged beyond repair, a cell’s natural defense is to kill itself, a process called apoptosis. Elevated levels of EGFR thwart this function. Therefore, chemotherapy drugs that are designed to trigger apoptosis in cancerous cells become ineffective.

The Georgia Tech researchers developed a nanoparticle therapy that uses a minute gel pellet to deliver short interfering (si) RNA to cancer cells. This siRNA is able to prevent the cell from starting the process to produce the protein for EGFR. “We’re knocking down EGFR at the RNA level,” McDonald said. “Since EGFR is multi-functional, it’s not exactly clear which malfunctions contribute to ovarian cancer growth. By completely knocking out its production in ovarian cancer cells, all EGFR functions are blocked.”

SOME TIME COMING

The researchers were able to see the efficacy of their method by using it to treat ovarian cancer in mice. By combining their siRNA with the chemotherapy drug cisplatin, they were able to reduce resistance to the medication and drastically shrink carcinomas or even eliminate them altogether. The plan to use the same nanohydrogel with other kinds of RNA to treat different types cancers.

Right now, the treatment is still at its very early stages and thus far the only in vivo trials have been on four mice. The law requires many more trials that show the treatment’s efficacy on animals before the researchers can move on to preliminary human trials, so we won’t be seeing this method used on people for quite some time. For now, it joins the growing number of nanoparticle treatments that could one day deal the final blow to the big C.

Bisphosphonates may hold potential for treatment, prevention of some cancers

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Bisphosphonates could potentially be repurposed for the prevention and adjunctive therapy of cancer driven by human epidermal growth factor receptors, according to research published in the Proceedings of the National Academy of Sciences.

Through connectivity mapping, researchers at the Icahn School of Medicine and the Tisch Cancer Institute, both at Mount Sinai, identified human epidermal growth factor receptors (HER) as a potential molecular entity for bisphosphonate action.

“Our study reveals a newfound mechanism that may enable the use ofbisphosphonates in the future treatment and prevention of the many lung, breast and colon cancers driven by the HER family of receptors,” Mone Zaidi, MD, director of the Mount Sinai Bone Program and a member of the Tisch Cancer Institute, said in a press release.

Mone Zaidi

Mone Zaidi

“Having already been approved by the FDA as effective at preventing bone loss, and having a long track record of safety, these drugs could be quickly applied to cancer if we can confirm in clinical trials that this drug class also reduces cancer growth in people,” Zaidi said. “It would be much more efficient than starting drug design from scratch.”

Zaidi, with Tony Yuen, PhD, also of the Tisch Cancer Institute, and colleagues from institutions around the globe used protein thermal shift and cell-free kinase assays, with computational modeling.

Bisphosphonates bind to the kinase domains of HER proteins, preventing abnormal growth signals from passing on; this includes the forms of the protein family making some tumors resistant to leading treatments, according to the release.

Results encompassed four types of tyrosine kinase receptors — HER1, HER2, HER3 and HER4 — that occur on the surfaces of cells, regulating division and proliferation.

Once a bisphosphonate-receptor connectivity map link was digitally detected, the scientists conducted experiments in cancer cell cultures that validated the potential of treating HER-driven cancers with the drugs alone and in conjunction with the approved tyrosine kinase inhibitor erlotinib (Tarceva, OSI Pharmaceuticals), according to the release.

The research was published with a second paper, by several of the same researchers at Mount Sinai and abroad, that examines repurposing of bisphosphonates for the prevention and therapy of non–small cell lung and breast cancer.

“While this finding is exciting, there is no business model for conducting the costly clinical trials that would be needed to repurpose bisphosphonates for cancer,” Zaidi said in the release. “Pharmaceutical companies are unlikely to pay for research to develop generic drugs where there is no chance of patent protection or profit, so we will be looking for a nontraditional funding source, perhaps the federal government.”