At present, many large hospitals in China have carried out targeted cancer therapy, and it can be said that targeted therapy has entered a new era. Compared with more than ten years ago, targeted therapy is more popular, and patients' demand for targeted therapy is also more and more, so is targeted therapy really a panacea for cancer? Today, we will talk about this topic for liver cancer.
As the mechanisms that cause normal cells to become cancerous and cause abnormal division and growth of cancer cells are gradually understood, research on targeted therapeutics has become one of the most important areas in the development of new cancer drugs. These drugs block the proliferation and spread of metastasis of cancer cells by attacking specific targets on cancer cells, and reduce the damage to normal cells, so that patients suffering from cancer can be treated with additional hope.
In clinical practice, targeted therapeutic agents are often contrasted with traditional chemotherapeutic agents. Chemotherapeutic drugs often target mechanisms of general cell growth regulation (e.g., DNA synthesis, control of cell mitosis) and are therefore less specific for cancer cells.
Targeted therapeutics target molecules or enzymes related to the cellular cancer process, such as cellular information transmission pathways associated with abnormal cancer cell proliferation or increased drug resistance, or regulatory mechanisms that promote abnormal tumor vascular proliferation and cancer cell metastasis. By inhibiting these abnormal mechanisms, we can achieve anti-cancer therapeutic effects. Therefore, the specificity of targeted therapeutic drugs is generally better than that of traditional chemotherapeutic drugs.
Targeted therapy for liver cancer, does it really work?
Let's take an example, for example, a targeted therapy drug for liver cancer is sorafenib. Sorafenib is a multi-kinase inhibitor that blocks the information transmission process related to the growth of cancer cells and vascular endothelial cells, and directly triggers apoptosis in liver cancer cells, while inhibiting tumor vascular proliferation, thereby reducing blood supply and slowing down the growth of cancer cells.
In previous large studies, patients with advanced hepatocellular carcinoma treated with sorafenib who were inoperable or receiving other curative treatments had a mean survival of 10.7 months, a significant increase of 2.8 months over the mean survival of 7.9 months in the placebo control group.
The same study of patients in Asia found a mean survival of 6.5 months for those treated with sorafenib and 4.2 months for those treated with placebo, which was also significantly longer by 2.3 months.
Both studies, conducted several years ago, showed that sorafenib was indeed effective in prolonging the survival of patients with advanced liver cancer. While this is certainly a long way from eradicating the tumor, it is the first time in history that a rigorous clinical trial has demonstrated that patients with hepatocellular carcinoma who are unable to undergo surgery or other curative treatments can be treated with a drug that prolongs their survival. Because of the success of the clinical trial of sorafenib, major pharmaceutical companies around the world have invested considerable resources in the research and development of new drugs for liver cancer, followed by a variety of related drugs, such as lenvatinib, cabozantinib, regorafenib, apatinib, etc., presenting a blossoming effect
How does targeted therapy differ from conventional chemotherapy?
Many people think that the so-called targeted therapy is to kill only cancer cells without attacking normal cells, while traditional chemotherapy is to kill both good and bad cells, this statement, in fact, has some conceptual misunderstandings and is not entirely correct.
In fact, chemotherapy is not an all-or-nothing treatment that kills both good and bad cells. Many chemotherapeutic drugs have their own mechanism of action and act on specific enzymes or molecules. However, the target of chemotherapy is mostly related to cell proliferation, such as the structure of DNA and cell division, so it is less specific. As long as the cells that proliferate faster in normal cells, such as hair, oral or gastrointestinal mucosa, bone marrow hematopoietic cells and other cells that proliferate and divide on their own, their sensitivity will be greater and they will be significantly affected.
Targeted therapeutic drugs, on the other hand, search for molecular enzymes related to the process of cellular carcinogenesis, including information transmission pathways, tumor-related angiogenesis, factors related to the regulation of cancer cell metastasis, etc. These are characteristics of cancer cells that are less likely to appear in normal cells, and the drugs developed according to this target are more specific, but not 100% will not affect normal cells, so targeted therapy will still have certain side effects.
Targeted therapy may be considered for advanced liver cancer
The staging of hepatocellular carcinoma is based on the size and number of the tumor, whether it invades the hepatic portal vein or has metastases outside the liver, abnormal liver function due to cirrhosis, and the patient's physical condition.
The treatments for hepatocellular carcinoma can be summarized into two categories: radical treatment and palliative treatment.
Open resection, embolization, and liver transplantation are all radical treatments, and patients with earlier stage liver cancer should prioritize these treatment modalities that have a chance to cure the tumor. Palliative treatments include arterial embolization, targeted drug therapy, etc. These treatment modalities can be considered if patients with liver cancer are no longer suitable for radical treatment such as open resection.
In general, patients with liver cancer who cannot undergo radical treatment can be divided into two categories.
If the number of tumors does not exceed 3 and the largest one does not exceed 3cm, liver transplantation can be considered. However, since the source of liver donation is not easy, usually the second best option is to use vascular embolization or targeted therapy.
The second group is those who have good liver function, but the number of tumors is too large or there are extra-hepatic metastases that cannot be removed, and even vascular embolization is not suitable, then targeted therapy can be considered. These two groups of patients are mostly intermediate and advanced stage liver cancer patients.
However, the use of targeted drugs is now being explored, and many medically developed countries may be using targeted therapies earlier, so many new drugs for liver cancer undergoing clinical trials will also include some patients with liver cancer that is still in the intermediate stage. In Asian countries, because of the large number of liver cancer patients, doctors are more skilled and experienced in surgical techniques and local treatment, and have a more aggressive attitude towards treatment, so targeted therapies are used mostly for patients with more severe disease.
Targeted therapy is not recommended in the first instance if the patient is a candidate for surgery or other radical treatment. For patients in the mid-stage, the difference in effectiveness between targeted therapy and other treatments is still being investigated. Whether using targeted therapy as an adjuvant treatment after surgery can reduce the chance of tumor recurrence is also being studied, but many medical institutions are already doing so, and there are some results.
For patients with advanced liver cancer, combining targeted therapies with conventional chemotherapy may increase the chance of controlling tumor growth, but the combination of the two may also increase side effects and therefore must be evaluated very carefully and the toxicity of the drugs controlled.
Treatment should be continuously followed up and evaluated during use
Targeted therapies are mostly taken orally and must be used according to standard doses, adjusted according to the patient's physical condition and side effects, and taken until it is confirmed that there is no improvement in the condition.
From past treatment experience, the chance of using a single targeted therapeutic agent to treat liver cancer that can cause significant reduction in tumor size is actually not high. The main effect is to slow down tumor progression and prolong survival time. Therefore, before using targeted therapy, it would be helpful to have a follow-up period to understand the growth rate of tumor through imaging (e.g. CT or MRI) and blood tests (e.g. methemoglobin) to evaluate the effectiveness of targeted therapy. After initiation, the doctor will adjust the dosage according to the patient's condition and liver function, and evaluate the possible efficacy with imaging and blood tests every 2 to 3 months.
Impact of targeted therapy on the quality of life of patients with liver cancer
Targeted therapy is more specific, but there may still be side effects. The more common ones include reactions such as increased skin sensitivity, swelling or dryness and blistering of the hands and feet, as well as skin rash, high blood pressure, diarrhea, and weakness and tiredness. Therefore, although targeted therapy may lead to longer survival and slower tumor progression in patients with advanced liver cancer, there seems to be no significant improvement in subjective quality of life.
In addition, targeted therapies may also develop resistance. If the growth of tumor continues to grow after a period of delayed use, it may be assessed whether resistance has developed and discontinuation may be considered.
If financial ability allows, is it true that the earlier a patient with liver cancer uses targeted therapy, the better the results? Can it be used to replace conventional chemotherapy?
The earlier the targeted therapy is used, the better the effect is, there is no empirical study to judge; and the choice of targeted therapy and chemotherapy must depend on the patient's condition, there is no replacement or use of sequential issues.
Can liver cancer be treated with targeted drugs even if it has metastasized to other organs?
Yes. Targeted therapy may also be tried for liver cancer that has metastasized to other organs or has invaded the hepatic portal vein.
Can targeted therapy cure liver cancer? Does it mean that advanced liver cancer patients are hopeless if even targeted therapy does not work?
Targeted therapy cannot cure liver cancer. The current study results only found that it can prolong the survival of liver cancer patients. Patients with advanced liver cancer may consider targeted therapy. If targeted therapy does not work, they may be evaluated by their physicians for other treatment options, and even with targeted therapy, there is more than one drug to choose from.
What should I pay attention to in my daily life for patients receiving targeted therapy?
Whether or not targeted therapy is used, patients should pay attention to balanced nutrition and normal lifestyle, especially it is best not to use health food or self-medication without permission, so as not to affect the metabolism and effect of the treatment drugs.
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