Ovarian Cancer Researcher Aims to Find New TreatmentSep 22, 2016
Earlier this year, individuals donated to CrowdRise to fund a promising young cancer researcher. With those crowdfunded dollars – plus additional support from the American Cancer Society – scientist Rebecca Wates, PhD, received a two-year grant of $111,500 to investigate ovarian cancer treatments. Here’s what she’s working on.
When it comes to ovarian cancer treatment, “there are three big downsides,” explains Rebecca Wates, PhD, a postdoctoral fellow at the University of Kansas Medical Center.
First: Surgery can only remove what’s visible, so very small tumors can be missed.
Second: Chemotherapy for ovarian cancer, which usually consists of a platinum drug and a taxane, is highly toxic, so it’s common to feel very sick from the drug’s side effects.
Third: Despite the success of targeted therapy in many cancers, Wates points out the limitations of a single-target drug for ovarian cancer. “These tumors are very diverse in their genetic makeup,” Wates says. “The primary tumor could be different than the spreading tumors. And recurrent tumors can be different from those two.”
With her grant from the American Cancer Society, Wates has a shot at changing the outlook for ovarian cancer – which has a relative 5-year survival rate of 46% and is the leading cause of gynecologic cancer deaths. The work she’s just begun will build on her previous research to find a treatment that is less toxic than current treatments, and yet kills a broad spectrum of ovarian cancer cells.
Source: Cancer Statistics Center, American Cancer Society
Two Genes Could Be Game Changers
Targeted drugs are designed to attack cancer cells while leaving most normal cells undamaged. There are 2 targeted therapies currently approved to treat ovarian cancer. One is Avastin (bevacizumab), which binds to a substance to inhibit tumor angiogenesis – the formation of new blood vessels, which is essential to help tumors grow and spread. Avastin can slow or stop the growth of tumors, but it doesn’t seem to help women with ovarian cancer live longer. The other drug is Lynparza (olaparib), a PARP inhibitor that’s approved for women with advanced ovarian cancer who also have BRCA gene mutations – a small proportion of patients. Lynparza blocks the PARP pathway, which makes it hard for cells with a mutated BRCA gene to repair themselves after chemotherapy. Like Avastin, it can slow tumor growth but doesn’t appear to extend survival.
Wates is investigating a different approach. She’s looking for a “a compound that kills the tumor based on something it needs to survive,” she says.
In previous experiments, Wates and colleagues deleted genes from ovarian tumor cells to find out whether the absence of any of them would kill the cells. They also conducted the same research on healthy ovary cells. “We were looking for a gene that, when deleted, caused ovarian tumor cells – but not normal ovarian cells – to die,” she says.
They were hopeful when they found that the gene KIF11 did just that, but they weren’t the first to make this discovery. When Wates searched the scientific literature on KIF11, she learned there are anti-KIF11 drugs in clinical trials. As it turns out, the clinical trial in ovarian cancer patients failed.
The protein that the KIF11 gene makes acts like a motor that helps cancer cells multiply. As Wates continued her research on the gene, she learned that when you take away KIF11 in ovarian cancer cells, a backup motor called KIF15 kicks in. Now she’s on the hunt for a drug to target KIF15.
The Next Two Years
Wates and her team will test existing compounds to learn if any target and inhibit KIF15. A specialized robot can add around 1,500 compounds, one by one, to plates containing the KIF15 protein in about 10 minutes. Wates plans to test over 200,000 compounds. “First and foremost, we want to know which of the compounds bind directly to KIF15,” she says.
Then, Wates and colleagues will test the compound along with an existing KIF11 inhibitor in ovarian tumor cells. Ultimately, she says, her goal is to “give the mice a drug [that inhibits KIF15 and KIF11], watch the tumors disappear, and then let the mice live and make sure the tumor doesn’t reappear.” If this works it could go on to clinical trials in people.