Tumor cell resistance to multiple chemotherapeutic agents is a major cause of tumor chemotherapy failure. Some tumor cells are intrinsically resistant to certain antitumor drugs and do not respond to the drugs used at the beginning, which is also the main reason why these tumors become refractory; some tumor cells become resistant to drugs to which they were sensitive after a period of treatment, which is called acquired resistance.
During tumor cell proliferation, some cells may mutate, resulting in changes in their morphology and biochemical properties, changing their sensitivity to drugs to drug resistance. Mutations can also be induced during radiotherapy or chemotherapy, so that drug-resistant cells appear more frequently.
And when tumors come in contact with chemotherapeutic drugs, sensitive cells in tumors are killed by drugs, tumors shrink in size and produce clinical efficacy, but then drug-resistant tumor cells proliferate, forming a population of mainly drug-resistant tumor cells; meanwhile, after long-term contact with antitumor drugs, the membrane transport function of tumor cells, detoxification mechanism to drugs, and the number of drug targets can be altered, which eventually leads to The formation of acquired drug resistance.
Clinical manifestations
Chemotherapy failure is not the same as the emergence of tumor drug resistance, and a distinction needs to be made between the presence or absence of a relationship with drug resistance, such as bleeding, infection, and organ failure, which can cause chemotherapy failure. Only when the causes of chemotherapy failure are correctly analyzed can targeted prevention and treatment countermeasures be taken.
For example, the efficacy of chemotherapy in acute leukemia is often related to the age and signs of the patient, and the frequency of drug resistance is high in those who are not in remission. Patients with acute lymphocytic leukemia aged 2 to 9 years are susceptible to long-term complete remission after treatment, and those older than 50 to 60 years have a low rate of complete remission. Patient signs include more pronounced enlargement of the liver, spleen, and lymph nodes, higher body temperature, immune insufficiency, lack of normal stem cells in the bone marrow, and even significant obesity, all of which have lower rates of complete remission.
Treatment of leukemia after drug resistance
1. Hematopoietic stem cell transplantation
The only established cure for refractory, relapsed acute leukemia is allogeneic hematopoietic stem cell transplantation. Of course, every effort still needs to be made to achieve complete remission with chemotherapy before transplantation, otherwise transplantation is less effective.
2. Intensive chemotherapy
For example, intensive chemotherapy with high-dose cytarabine for acute myeloid leukemia and medium- and high-dose methotrexate for most acute lymphoblastic leukemia should be pursued as soon as complete remission is achieved and conditions for allogeneic hematopoietic stem cell transplantation are met.
3. Selection of new high-efficiency, low-toxicity chemotherapeutic agents
For example, a regimen with fludarabine as the core drug can be used, often in combination with cytarabine, both of which have synergistic effects. Granulocyte colony-stimulating factor (G-CSF) is also added to mobilize leukemic cells from quiescence into the cell cycle to increase sensitivity to chemotherapeutic agents. Allogeneic hematopoietic stem cell transplantation should likewise be pursued after remission.