“I’m about two months away from discovering if there are any other drugs and combinations that could save my life,” says Silverman, who has been taking targeted medicine based on her. detecting a mutation in the PIK3CA gine. It is unclear whether this drug reduces lung lesions. “If they could stop what was going on in my lungs, my life would be saved – or at least long,” he says of Vivan Therapeutics.
The basic science behind Vivan Therapeutics goes back to 1918, when Mary Stark, a lesser-known scientist in the famous Fly Room, biologist Thomas Hunt Morgan at Columbia University announced tumors in Drosophila larvae and try to put pieces of them into healthy larvae. Over the decades, the low-fruiting fly has become a very popular model of human disease. (Morgan won a Nobel Prize for his Drosophila work in 1933.) The Fruit Fly reveals effects and cures for disorders from amyotrophic lateral sclerosis to aging, from epilepsy to eye disease – ample source of search for a book titled First in a fly. (The author, Harvard geneticist Stephanie Mohr, also contributes to an ongoing blog called Drosophila models of human diseases.)
When the Drosophila melanogaster genome sequencing in 2000 (three years before the human genome), new opportunities arose for studying the genetic origin of disease. Developmental biologist Ross Cagan was studying cancer mechanisms in fruit flies, but in 2010 he turned the question around: Could the flies show cancer-killing drugs, even if science hadn’t worked out? out completely?
He created the drug testing process in his laboratory at Mount Sinai Medical Center in New York City that has since been licensed by Vivan Therapeutics. “We’re looking at what drugs work, attacking the cancer network with a therapeutic network,” said Cagan, who recently transferred his work to Glasgow University in Scotland.
First, scientists examine the patient’s tumor, comparing its exome and the patient’s entire exome layer of blood to identify the protein coding changes of the tumor. They select the changes that are likely to guide the growth or growth of the tumor, based on the action or location. (One tumor can contain hundreds of genetic variations, but usually only five to 15 of them control growth.)
“There are many, many tumors that are not caused by a single mutation. Or one mutation is exacerbated by two or three others that allow the cancer to grow, multiply, and survive, ”says Marshall Posner, a Mount Sinai oncologist who specializes in treating head and neck cancer. fly by Cagan but not affiliated with the company.
Scientists next inject layers of synthetic bacterial DNA into the larvae of fruit flies to inject the mutations into the genome. The situation is detailed; colorectal cancer is expressed in squamous cell carcinoma, e.g. They then capitalize larval development by changing the temperature of their environment, so the tumor is in time to kill the larvae in seven days. (Larvae usually metamorphose into flies in 10 to 11 days.)
Then these fruits have to multiply “avatars”. Vivan Therapeutics uses approximately half a million fly larvae to test approximately 2,000 drug and drug combinations, including a version of most FDA-approved drugs currently in use, said the company ‘s chief scientific officer, Nahuel Villegas. For example, an anti-inflammatory or anti-hypertensive drug may have invisible cancer-fighting properties when used with a tumor suppressor.
The larvae live in tubs in groups of 35 – half with the eardrum, half without the control group – feeding on food with drugs. The healthy larvae are altered by genetic changes that make them shorter and fatter, so they can be different from those that carry tumors. After seven days, their survival rates are compared. All drugs are tested on at least 300 larvae, and a promising combination of drugs has been retested. The main candidates are ranked according to the survival rates, but ultimately the selection takes into account the clinical history of the human patient and the diagnosis of the oncologist. For example, a patient with an underlying heart problem may steer clear of a drug related to heart concerns, Villegas says.