A new method of selecting anti-cancer drugs

Julia Korowski, XX2 CENTURY, based on MIT materials: A new strategy for choosing cancer drugs

Choosing a drug for the treatment of a cancer patient is, to put it mildly, not an easy task. Medications that help some are useless to others, and tumors that initially succumb to treatment can eventually develop resistance to medications. Researchers from the Massachusetts Institute of Technology (Massachusetts Institute of Technology) have developed a new method for assessing the sensitivity of tumors to drugs. The results of the work are published in Nature Biotechnology (Stevens et al., Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate – VM).

Previously, scientists tried to find genetic markers of tumors that signal sensitivity to targeted anti-cancer drugs. However, they are found only in some types of cancerous tumors, and even in cases where it is possible to conduct a test, it does not always give accurate results.

MIT researchers have taken a different approach. They were partly inspired by the antibiotic resistance test, which doctors have been using for several decades in the treatment of bacterial infections. During this analysis, biological material (for example, blood or urine) containing the necessary microorganisms is taken from the patient, bacteria are placed in a nutrient medium and exposed to various types of antibiotics. If bacteria die, they are sensitive to drugs, if they continue to multiply, they have developed resistance. Scientists decided to go a similar way: to track the reaction of tumor cells to the drug.

For the past few years, the laboratory of Professor Scott Manalis has been developing a device called a suspended microchannel resonator (SMR). It can measure the mass of a cell 10-100 times more accurately than any other device and allows you to correctly calculate the rate of cell growth. The scientists analyzed different subtypes of glioblastoma and leukemia cells that were sensitive or resistant to certain drugs – MDM2 inhibitors and BCR-ABL inhibitors. This allowed them to understand whether the new approach gives accurate predictions.

The researchers exposed tumor cells to anti-cancer drugs. The SMR measured the mass of each cell every 15-20 minutes, and after 15 hours the scientific team had enough data to calculate the rate of mass gain. Cells sensitive to drugs slowed down growth, which affected the mass, and tumors that developed resistance continued to grow at the same rate. "We have shown that cells that we knew were sensitive to therapy grow much slower than those that are resistant to it," says lead author of the study Mark Stevens (Mark Stevens). "And since the cells are still viable, we have the opportunity to continue studying them after the measurement."

Recently we published a note about a similar method for determining the sensitivity of microbes to antibiotics using a microfluidic cantilever – VM

One of the advantages of the new method is that it does not require a large number of cells. During experiments with leukemia, scientists were able to obtain accurate results using a small drop of blood containing about 1,000 tumor cells. Another plus is that the device allows you to make quick measurements. Now that it has become clear that the method works, scientists intend to use it to understand why some tumors develop resistance. They determine the sensitivity of cells, and then sequence their RNA to find out which genes are "turned on". "Now that we can identify which cells are not responding to therapy, we can isolate and analyze them to understand how the resistance mechanism works," says Manalis.

Glioblastoma multiforme is the most frequent and most aggressive form of brain tumor, which accounts for up to 52% of primary brain tumors and up to 20% of all intracranial tumors. Despite the fact that glioblastoma is the most common primary brain tumor, only 2-3 cases of the disease are registered per 100,000 inhabitants of Europe and North America.
Acute lymphoblastic leukemia is a malignant disease of the hematopoiesis system, characterized by uncontrolled proliferation of immature lymphoid cells (lymphoblasts). This is the most common malignant disease in childhood and adolescence, the peak incidence occurs at the age of 1 to 6 years.

Portal "Eternal youth" http://vechnayamolodost.ru  11.10.2016