Science

Drug resistance has become a "roadblock" to targeted therapy! How to determine drug resistance? What happens after drug resistance?

What is targeted drug resistance?

Targeted therapy is an important approach to cancer treatment nowadays, especially for lung cancer, and most of the new lung cancer drugs are targeted drugs. The emergence of these new targeted drugs has significantly improved the treatment effect of lung cancer and prolonged the survival time of lung cancer patients.

Drug resistance has become a "roadblock" to targeted therapy! How to determine drug resistance? What happens after drug resistance?

However, the mechanism of action of targeted therapy is still essentially targeting a certain protein or a certain molecule of cancer cells to inhibit the growth of tumor cells. However, cancer cells are "cunning", once they find that they can no longer walk on this path, they will choose to find another way, such as genetic mutation, and the drug will no longer work, which is what we call drug resistance. Even though there is a gene mutation target before, but the targeted drugs do not work, the disease progress is this reason.

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Three scenarios of targeted drug resistance

1、Slow drug resistance

Take a lung cancer patient as an example, during the period of taking the targeted drugs, the blood check reveals that the tumor markers rise, but the imaging examination suggests that no tumor enlargement is found, in this case, we suspect that slow drug resistance has occurred, but in this case, we do not recommend to stop the drugs. We should know one thing: tumor markers can only be used as dynamic reference indicators, while imaging is the "gold standard" to judge whether the disease is progressing. After slow drug resistance, we should not rush to change the drug, but should consider the next treatment plan according to the individual situation and the instructions of the treating doctor.

Drug resistance has become a "roadblock" to targeted therapy! How to determine drug resistance? What happens after drug resistance?

There is also a situation where some patients are taking targeted drugs and one or more lesions throughout the body progress very slowly, with a few centimeters of tumor growing only a fraction of a centimeter for most of the year. This may also be a case of slow drug resistance. If this happens, we suggest to continue to take the previous targeted drugs, rashly stopping them may lead to "explosive" tumor progression, but depending on the patient's condition, we can choose to combine a mild, single-agent chemotherapy or anti-angiogenic targeted drugs to control tumor growth.

2、Partial drug resistance

Or take lung cancer patients as an example, when taking targeted drugs, regular review reveals great tumor control and significant tumor shrinkage, but metastases from other sites are found, such as rare brain metastases and bone metastases, then this condition is presented with partial drug resistance. Generally, we still do not recommend to discontinue the targeted drug treatment, and we can choose to carry out local targeted treatment for these metastases, such as for brain metastases, we can take measures of gamma knife radiotherapy or whole brain radiotherapy according to the size of the lesion; for bone metastases, we can take injection of zoledronic acid or also local radiotherapy for the metastatic lesion, etc.

Drug resistance has become a "roadblock" to targeted therapy! How to determine drug resistance? What happens after drug resistance?

3、Total drug resistance

In the last 30 days of continuous administration of targeted drugs, the review visually revealed a significant increase in tumor size, a systemic and multiple progression, such as a significant elevation in markers and even metastasis to other sites, and a significant change in physical sensation, such as pain, cough, and dizziness. At this time, it means that the targeted drug is no longer effective for lung cancer, and this targeted drug should be stopped to avoid delaying the treatment time. At the same time, a second biopsy can be performed to see if new drug-resistant mutations have been generated. Based on the biopsy results and genetic testing, you can choose whether you need targeted therapy, chemotherapy or other treatment options.

Drug resistance has become a "roadblock" to targeted therapy! How to determine drug resistance? What happens after drug resistance?

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What should patients who have developed drug resistance do?

In case of resistance to a targeted drug, we generally have four options: reintroduction of chemotherapy, re-doing pathology testing, re-testing genetically, or simply switching to a new targeted drug with a higher generation. Of these four routes, I would recommend genetic testing the most. Targeted therapy is a precise treatment for the mutated gene, if you do not have genetic testing, you can change your treatment plan at will, and there is a high risk of ineffective treatment and delayed treatment.

Drug resistance has become a "roadblock" to targeted therapy! How to determine drug resistance? What happens after drug resistance?

In EGFR-positive non-small cell lung cancer patients, for example, the most common drug-resistant mutation is the T790M mutation, which occurs in more than 50% of patients and results in resistance to a generation of targeted drugs. In this case, we suggest patients to do genetic testing again to monitor whether the T790M mutation has occurred, and if so, we can switch the targeted drug to third-generation Ocitinib (Teresa), which is a targeted therapy developed specifically for T790M mutation resistance, so that they do not need to go through many "detours" and seek other