Tumor cells are too cunning, the best drug for cancer treatment - how targeted drugs are completely ineffective
Since the first targeted drug Rituxan came out, the development of targeted drugs has a history of 23 years. Targeted therapy breaks through the three traditional treatment modes, which is a very big progress in the field of tumor treatment in recent decades. It brings survival benefits to many patients, and even a few patients achieve long-term tumor-bearing survival. However, targeted drugs are not magic drugs. Like chemotherapy drugs, drug resistance will also occur. For example, oral small-molecule targeted drugs for lung cancer usually develop drug resistance in about half a year to a year, and intravenously used monoclonal antibody-based targeted drugs will also develop drug resistance.
The reasons for drug resistance to targeted drugs start from the pathogenesis of cancer. Cancer cells are formed due to the mutation of normal cell genes under the action of various carcinogenic factors. Cancer cells proliferate unrestrictedly, and do not have the structure and function of normal cells. They frantically rob normal cells of nutrients while destroying normal tissues and cause systemic spread and metastasis. .
There is not one gene that causes cancer cells, and dozens of gene mutations that may cause cancer have been found. Each cancer cell may have one or several mutations at the same time, and among these mutations, some mutations are dominant, and some mutations are weak. We have detected a dominant mutant gene, and if there is a targeted drug against this gene, the treatment effect is expected to be very good. But cancer cells are very cunning. When the dominant gene is suppressed, other non-dominant genes turn into dominant genes, and the cancer cells can grow again, so the clinical manifestation is that the tumor shrinks first, and then grows again after a period of time.
Another reason is the heterogeneity of tumors. Tumor It is a mixed population of cells, in tumor tissue, almost no two cancer cells are exactly the same, just like no two leaves are exactly the same in the world. Some tumor cells carry this target gene, and some tumor cells do not have the target gene. Targeted drugs have obvious killing effects on tumor cells with the target gene, which can cause tumor death or apoptosis, but without these The tumor cells of the target gene still survive because they are not inhibited by the outside world. At the beginning, this part of the cells may account for a small proportion, but over time, drug-resistant cancer cells gradually proliferate and enrich, and gradually manifest a clinically observable and measurable drug resistance phenomenon.
At the same time, the genes carried by tumor cell clusters will undergo dynamic changes, especially after the use of targeted drugs. For example, after the use of a first-generation targeted drug in patients with EGFR-mutant lung adenocarcinoma, 50% of patients will develop EGFR T790M mutation. Patients can choose the third-generation targeted drug osimertinib. C797X mutation, MET gene amplification, etc. will occur after oral osimertinib for a period of time.
So far, there is no targeted drug that is not resistant to resistance in all cancer patients. When the targeted drug is resistant, we can only re-detect the sensitive gene targets and switch to other targeted drugs, which is a bit like fighting monsters in a game. , to keep changing equipment, or you may be killed by monsters. In short, cancer cannot rely on only one method, one drug, and the comprehensive treatment model will never be out of date. The combination of targeted and traditional therapy or the combination of target and target may be the mainstream treatment method in the future.
#cream of the crop#