At present, precision medicine has become the trend of cancer treatment, but for cancer patients, it is difficult to accurately select the appropriate drugs; for cancer drug R&D companies, it is a long process to develop new cancer drugs, and what’s worse, there is a lack of evaluation methods that can realistically reflect the true clinical efficacy of a drug.
i-CR® system is a high-throughput drug screening platform that is closer to the individual conditions of cancer patients. The principle of this technology is to turn fresh tumor tissue into primary tumor cells that can proliferate in large quantities, and use a high-content fluorescence microscopy system to observe the effects of drugs on the cells. They serve as surrogates for patients to test the effects of anti-tumor drugs.
In a recent interview with Dingxiangyuan, the general manager of Percans Oncology Yihai “Felix” Lin introduced the company's self-developed i-CR® in vitro drug susceptibility screening technology and its important role in the development of new cancer drugs.
Left:Founder of Cothera Bioscience Dr Chen Yiyou Right:General Manager of Percans Oncology Lin Yihai
Innovation on New Drug Development - Exploring Synergistic Effects of Multiple Drug Molecules
The development of anti-tumor drugs is a complex and time-consuming process. Percans Oncology focuses on exploring the synergistic effects of multiple drug molecules and finding new indications. It has been widely accepted that cancer drugs often don’t work well alone, but combinations of multiple molecules may produce stronger effects due to mutual synergy, such as AIDS cocktail therapy. Percans Oncology’s high-throughput i-CR® in vitro drug susceptibility screening platform (i-CR® system for short) allows one to directly explore the synergistic effects of different drug combinations in vitro.
i-CR® In Vitro Drug Susceptibility Screening Technology Platform - The Key to Innovation
i-CR® system plays an important role in the drug development.
First of all, it is very important to predict the drug efficacy. Many clinical trials have failed due to the lack of effective pharmacodynamic experiments and data.
Secondly, the i-CR® system cultivates primary tumor cells from patients, which resembles more closelyto patients’ tumors than traditional tumor cell lines. i-CR® system showed excellent consistency with patients clinical outcomes, and the accordance rate between i-CR tests and clinical responses is above 80%, making the drug efficacy judgement more accurate and clinically relevant. In addition, in the process of in vitro tumor cell culturing, a variety of system indicators can be used to evaluate the survival and growth of tumor cells, and specific markers can be used to identify different types of cells. Therefore, the relationship between tumor cells and drug efficacy can be examined with more comprehensive information.
2. For the development of new drugs, screening a large number of primary cells preclinically can produce a more reliable prediction of drug efficacy. The cells can be distinguished under a microscope according to their relative drug resistance. An accurate drug response profile can therefore be obtained for the entire tumor cell population.
Traditional tumor cell line models rely on the determination of IC50 to judge the efficacy of a drug, while i-CR® system can provide more detailed information. Our previous study showed that only when a drug achieves an in vitro tumor inhibition rate of more than 90%, can it have a significant therapeutic effect, or the tumor is prone to recurrence. Common chemotherapeutic drugs can inhibit tumors up to 70-80%. Although they can inhibit the tumor growth for a short period of time, they fail to clear the tumor cells completely and meanwhile the adverse effects greatly damage the patient’s immune system. Therefore, patients treated with chemotherapeutic drugs are prone to cancer recurrence.
Thirdly, i-CR® system is suitable for many types of cancer. Different cell culture media shall be prepared for different cancers, because the cellular origins and growth characteristics vary with each type of cancer. At present, the success rate of culturing the best primary cells for colon cancer can reach more than 90%; the success rate of culturing cancer cells such as lung cancer and liver cancer is about 60%; the culture system of each cancer is still being optimized
Meanwhile, it is necessary to control the cells not to differentiate during the proliferation process, which is one of the technical difficulties. Percans Oncology has launched scientific research or clinical research cooperation with Peking University Cancer Hospital, Cancer Hospital Chinese Academy of Medical Sciences, Peking University People's Hospital and Aerospace Aviation Hospital through i-CR® technology. The data of the cooperated studies have verified the clinical application value of i-CR® system and the results will be published soon.
Discovery of New Drug Combinations
i-CR® system has been successfully applied to the screening of combination drugs for colon cancer. We have discovered that the combined inhibition of three drug targets showed a significant synergistic therapeutic effect on patients with advanced colon cancer. Each of the three targets has corresponding therapeutic drugs that have been approved by the FDA. In the project, we selected patients with advanced colon cancer who were refractory to the first-, second-, and third-line drug treatments, and used the triplet combination to test the patients' primary cells. And we found that single target inhibitors had very moderate inhibitory effects on the cancer cells; but theinhibition rate could reach more than 90% in most of the cases and the highest inhibition rate could reach >99% if the triplet combination was used. We have applied for an international patent for this drug combination and are preparing for a phase I clinical trial.
The successful research experience in colon cancer can be extended to screening for more effective combinations. Cancers like liver cancer and pancreatic cancer can be treated with similar approaches. Our company is strived to find more novel combinatory uses of targeted drugs to fight cancer.
Dozens of drug targets have been discovered in the scientific community. There may be a synergistic relationship between signal pathways of different targets, and there may be also a synergistic effect between the upstream and downstream of the same signal pathway. Therefore, blocking a single signal pathway may not kill tumor cells completely, and blocking two or more signal pathways at the same time has a better killing effect on tumors. Searching for such drug combinations requires screening a large number of patient primary cells, and i-CR™ system can be a great tool for this. This is a method of re-creation, repurposing old drugs to seek better tumor treatment, and is of great significance for tumor patients.