Israeli startup finds way to predict tumor resistance to chemo

Chemotherapy is sometimes thought to be a treatment that’s harsher than the disease it comes to fight.

Cancer patients are subject to rounds of chemotherapy treatments in which cells – both healthy and cancerous are expected to be destroyed in the process.

So it’s especially awful when the targeted tumors have cell mutations that are resistant to chemo or develop resistance afterwards, rendering the potentially harmful therapy ineffective and pointless.

Now Hebrew University researchers say they have developed a way to predict resistance to chemotherapy treatments, which can help doctors and patients better target their treatments and helping reduce the rate of resistance levels “dramatically,” from the current 50 percent.

NewStem, a new biotech company set up by Prof. Nissim Benvenisty of the Azrieli Center for Stem Cells and Genetic Research at the Hebrew University of Jerusalem, says it discovered and managed to harvest human pluripotent embryonic stem cells which have just one set of chromosomes — called haploid cells — as opposed to the diploid cells with two sets of chromosomes that are found in most human cells. These pluripotent stem cells have the ability to become any cell type, for example heart cells or brain cells.

Using these newly found and harvested haploid cells, the researchers created a so-called “cell line” in which a small number of cells are proliferated. They then mixed these cells with an existing genome-editing technique called Crispr Cas, which causes genetic mutations, managing to create a library with 180,000 mutations in 18,000 genes — or on average 10 mutations per gene.

“This would cover all relevant genes for therapeutic purposes,” said Ayelet Dilion-Mashiah, CEO of NewStem.

The company can then “take chemo treatment and introduce it to the library of mutations and see if all of the cells die. There will be some cases in which some cells survive and proliferate. It means that those cells have mutations that will cause resistance to the chemo. For persons with these kind of mutations, we will recommend not to use that specific chemotherapy treatment, since it will not be effective,” Dilion-Mashiah said. “We will be able to say if a tumor has mutations that make it resistant to specific chemo.”

So when the company receives the genetic makeup of the cancer of the patients, something that is regularly performed in course of treatment, it can see if that particular kind of cancer has the mutations that make it resistant to that particular chemotherapy plan, and make suggestions accordingly.

Based on these diagnostic capabilities, physicians will be able to better target the chemo to the patient tumor’s mutation characteristic, she said. “In this way, by reducing dramatically the resistance rate, we will increase the efficacy of the treatments.”

The company, recently founded as a spinoff of Yissum Research Development Company of the Hebrew University of Jerusalem, the technology-transfer company of the Hebrew University, is now raising funds to further develop a diagnostic kit based on the research execute clinical trials.

“We are hoping that the product will be in the market within three years,” Dilion-Mashiah said.