"Tumor in a Petri dish" will increase the effectiveness of breast cancer treatment
One of the tragic features of cancer is the fact that the drugs used for its treatment are highly toxic, and their effectiveness varies in a significant range from patient to patient. However, the new "tumor in a Petri dish" technology developed by Vanderbilt University researchers will make it possible to change things due to the ability to quickly assess the effectiveness of combinations of antitumor drugs on the patient's tumor cells before the start of chemotherapy.
According to the American Cancer Society, breast cancer ranks second in cancer mortality among women, second only to lung cancer. The primary treatment protocol for this disease depends on the results of the biopsy used to determine the type of tumor. The effectiveness of treatment is evaluated after 2-3 months by the dynamics of the size of the tumor focus. At the same time, from 33% to 43% of tumors do not respond to standard therapeutic protocols, and women have to be transferred to alternative combinations of drugs.
To date, doctors have at their disposal more than 100 different antitumor drugs, but only 10-15 of them are used in routine work. According to the head of the study, Professor Melissa Skala, the developers hope that the new technology will significantly increase the survival rate in breast cancer by selecting the most effective and least toxic chemotherapy option for each patient.
Traditional methods of tumor cell cultivation involve the creation of a monolayer of cells that behaves quite differently from the original tumor. Therefore, to study the patterns of malignant growth, researchers are developing technologies for cultivating three-dimensional tumor organoids, the patterns of behavior of which reflect the behavior of the original tumors.
The first stage of the new "tumor in a Petri dish" method consists in crushing the tumor tissue removed during surgery or biopsy into small fragments and placing them in a special collagen gel. Such conditions ensure the preservation of the three-dimensional structure of the tumor, including auxiliary cells of its microenvironment.
To assess the metabolic activity of tumor organoids, a method known as optical visualization of metabolic processes is used. To do this, a laser is used tuned to a frequency that causes two main cellular enzymes to fluoresce. Evaluation of variations in the intensity of this fluorescence provides dynamic information about cellular metabolism, which is a sensitive biomarker of the cell's response to drugs. The use of this test makes it possible to evaluate the reaction of tumor organoids to therapy within 24 hours. At the same time, the size of organoids sensitive to therapy begins to decrease within 72 hours.
Professor Skala notes that the new method does not require large financial and time costs. Moreover, it is suitable for high-throughput screening and can be used for simultaneous testing of dozens of drugs or their combinations.
Organoids from human tumor cells responding to therapy,
begin to decrease within 72 hours (below);
stable organoids (above) they continue to grow.
The method also allows us to evaluate the reaction of each individual cell of the tumor organoid. This point is very important, since tumors differ from each other, and their constituent cells may respond differently to therapy. If the drug destroys only 90% of tumor cells, the remaining 10% of cells can form a new treatment-resistant tumor.
The developers have already tested their method on mice and on six samples of human tumors using four chemotherapy drugs traditionally used for the treatment of breast cancer, as well as two experimental drugs. The next stage will be testing more human tumors and comparing the results with patients' reactions to therapy. The authors hope that if the data obtained will allow validating the results of the new test, clinicians will be able to use it in 5-10 years.
Fluorescent images of breast cancer organoids demonstrate the level of metabolic activity, in particular the mechanisms by which cells receive the energy they need to divide. The blue color corresponds to a low level of activity, and the orange color corresponds to a high level.
The top two images show organoids from mouse breast cancer cells treated with the antitumor drug trastuzumab. The fact of the predominance of blue color indicates that the drug suppresses their growth.
The two lower images show organoids consisting of two different types of human breast cancer cells: thrice-negative – on the left and expressing estrogen receptors – on the right.
After the validation of the method for breast tumors, the developers plan to expand its capabilities to predict the results of pancreatic cancer therapy. This disease is quite rare, but it is characterized by an exceptionally high mortality rate, accounting for 7% of the total mortality from cancer.
Article by Alex J. Walsh et al. Quantitative Optical Imaging of Primary Tumor Organoid Metabolism Predicts Drug Response in Breast Cancer is published in the journal Cancer Research.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Vanderbilt University materials:
Improving breast cancer chemo by testing tumors in a dish.
31.10.2014