There are no two identical leaves in the world, and no two identical cancers. Fundamentally speaking, cancer is a genetic disease. Cells have mutations due to various genetic factors or acquired stimuli. Some mutations change the pathways involved in regulating cell growth and interacting with the tissue environment, causing malignant cells that cannot be controlled proliferate and eventually become a cluster of cancer cells.

Scientists have identified a set of specific tumor DNA changes. Therefore, cancer patients no longer choose chemotherapy drugs based on pathological classification, but can find mutation sites through genetic testing, and formulate more effective chemotherapy for patients with fewer side effects, targeting, immunotherapy, and family cancer risk assessment. It has to be said that the era of individualized diagnosis and treatment for a patient with a set of plans has arrived. All cancer patients need a genetic test report in addition to a pathology report.

What is genetic testing?

Some people say that studying genes is studying the origin of life, because genes are the genetic material of life. Everyone’s genes are imperfect. Scientists once predicted that if there is gene repair technology to repair all the defective genes in the human body, then people will become "gods", but this is just an illusion, except for some normal genes in the human body. There are also some mutant genes, and the birth of cancer cells is that this part of the mutant genes is activated. These mutant genes may be missing, may be duplicated, or may be skewed... Moreover, through genetic testing, we can be precise find out these mutant genes, and then use various medical methods to treat and repair these mutant genes.

For example, many patients with advanced lung adenocarcinoma, most of them carry EGFR, ALK, ROS-1, BRAF and other gene mutations, and at this time, you can try targeted drug therapy, with high efficiency, low side effects, and relatively long survival. I have even encountered many cancer patients who have used targeted drugs combined with traditional radiotherapy and chemotherapy, and the survival period exceeds 10 or 20 years.

Who needs genetic testing?

All cancer patients can receive genetic testing; specifically, different diseases, different stages, for different purposes, and different patients are suitable for different genetic testing. For example, a patient with advanced lung adenocarcinoma has not received any treatment and has a poor family background. Just to find out whether there are targeted drugs that have been marketed in the mainland are available, and then only the most common genes need to be tested.

For another example, a wealthy boss who also has lung cancer has no effect on other medications. He is not reconciled and wants to try his luck to see if there are any targeted drugs available, whether it is domestic or foreign, whether it is already on the market or at the stage of clinical trials. At such moment, he may have to choose as many genes as possible, dozens, hundreds, or even all of the genes across cancer species. For this purpose, there are 451 genes of the whole cancer species, those containing the neoantigen 811 gene, and even the whole exome (more than 30,000 genes).

Is genetic testing necessary to take targeted drugs?

In fact, it is not. Anti-angiogenesis targeted drugs do not necessarily require genetic testing, because it is not known which or several gene mutations are related to the efficacy of these drugs. Such as anlotinib, lenvatinib, regorafenib, sorafenib, apatinib, sunitinib, cabotinib, cediranib, bevacizumab and other targeted drugs.

After a period of treatment, should patients re-do genetic testing?

In fact, the genes in tumor tissues are undergoing new mutations all the time, and the process is completely random. Various treatments may affect the frequency of mutations. That is to say, it used to be mutated once per 100,000 cells per day, but now it has become mutated once per 10,000 cells per day. Through the treatment of drugs, it is possible to screen and enrich drug-resistant cells with certain genetic characteristics, but in most cases, these drug-resistant cells lack effective new drugs, that is, after a period of treatment, it may indeed happen genetic changes, but there is no better treatment option.

Therefore, it is generally recommended only for patients who have received targeted therapy. After drug resistance and disease progression, genetic testing should be considered again as appropriate-because after targeted drugs have been used for a period of time, drug resistance will be developed, and some patients will be enriched. There are new mutations available for newer targeted drugs. For example, patients with advanced lung adenocarcinoma who took the first-generation targeted drugs (Iressa, Chemera, Tarceva, etc.) may have EGFR exon 19 deletion mutations at the beginning. After drug resistance, about half of the patients, There will be a new drug resistance mutation-EGFR T790M mutation, and there are already third-generation drugs such as osimertinib that can deal with this mutation. In this case, it is strongly recommended to perform genetic testing after drug resistance.

If a gene mutation is detected, is there a target drug available?

In fact, it is not! There are too many types of gene mutations, and most gene mutations are currently unclear whether they are related to tumors; most of them can be clearly related to tumors (such as P53 mutations, KRAS mutations, MYC amplification, etc.), there is no targeted drug that has been marketed. Therefore, gene mutations often occur, and a report with dozens of hundreds of pages is obtained, which clearly lists a few or even a dozen gene mutations, but there is still no suitable and marketed targeted drugs to choose from. If it is NTRK1/2/3 fusion, RET mutation or fusion, BRCA mutation, dMMR detection related mutation (MLH1/PMS2/MSH2/MSH6), MET mutation or amplification, MDM2 amplification, NARS mutation, or other special mutations, you can strive to participate in appropriate clinical trials.

What genetic test should do if PD-1 needed?

At present, genetic testing can also guide the choice of immunotherapy. For example, patients with MSI-negative but POLE gene mutations are also suitable for PD-1 inhibitors; while patients with EGFR mutations, JAK2 mutations, LKB1 mutations, and MDM2 mutations seem to be unsuitable for PD-1 inhibitor therapy. In addition, many studies suggest that the total number of mutations in tumor tissues, that is, patients with higher tumor mutation burden (TMB), the higher the effective rate of using PD-1 inhibitors.