What are the tests for lung cancer genetic testing?

  Lung cancer has become one of the leading causes of cancer deaths in human beings, and in China, lung cancer is the cancer with the highest incidence rate, exceeding 20% of the causes of cancer deaths, and the incidence and mortality rates are growing rapidly. Surgical resection is the best treatment for lung cancer, but most patients are already in advanced stage when they are first diagnosed with lung cancer and lose the opportunity of surgical treatment. Systemic chemotherapy is the preferred treatment for most patients, but a considerable number of patients give up further chemotherapy due to the poor effect of chemotherapy, and chemotherapy tolerance is the main reason for treatment failure. With the development of genomics, the application of genetic testing technology in early diagnosis of lung cancer and individual drug sensitivity and resistance detection is increasingly important. Let’s take a look together.  These abnormal changes often precede the appearance of clinical symptoms and become molecular markers of early lung cancer to a certain extent. Therefore, the relevant genetic tests are of practical value for the screening of people with high lung cancer risk, especially those with family tendency or heavy smoking with airway obstruction. Moreover, some of the genetic abnormalities in these precancerous lesions or mild atypical hyperplasia are reversible, and early diagnosis and guiding patients with precancerous lesions away from carcinogens or chemical interventions may reverse the further development of precancerous lesions. Currently, the clinical diagnosis of lung cancer is based on genotypic alterations of lung cancer, which are not highly sensitive, appear late, and have limited value in the early diagnosis of lung cancer. Therefore, the target of lung cancer treatment is gradually shifting from patients with clinical symptoms at intermediate and advanced stages to patients with asymptomatic early stage or precancerous lesions, which is the current change in the concept of lung cancer treatment.  Currently, detection of epidermal growth factor receptor (EGFR) mutations and concurrent lymphoma kinase (ALK) rearrangements is widely used for screening of non-small cell lung cancer, and second-generation sequencing technology will provide more genetic information about the cancer. ngs can find disease-associated genetic variant loci in therapeutic regimens. NGS may be able to find disease-associated genetic variants by screening for heterogeneous malignancy-associated mutant loci when no other test can tell what caused the patient’s disease. NGS sequences multiple loci instead of a single locus test, making better use of samples to reduce the number of samples taken. For lung cancer testing, one difficulty is the acquisition of test tissue. Patients only need to send a small amount of tissue to one laboratory; there is no need to perform surgery to cut large amounts of tissue to send to different laboratories. A recent study has shown that only one blood test is needed to predict how well small cell lung cancer patients respond to therapeutic agents, and that testing circulating tumor cells can accurately predict the effect of lung cancer chemotherapy. Obtaining tumor samples from lung cancer patients through biopsy techniques is difficult because it is difficult to reach the tumor site, and the samples obtained are often too small to reveal useful information about how to best treat the patient. Liquid biopsy provides a viable method of obtaining tumor samples, and liquid biopsy can provide a rapid understanding of the disease from a blood sample. Of course, liquid biopsy technology is also applicable to the early diagnosis of lung cancer. In addition, genetic testing is the same cost as traditional single site testing and does not increase the burden on the patient.  About targeted drug genetic testing, molecular targeted drug therapy is regarded by many patients as the first ray of hope for lung cancer treatment because it is highly selective in killing tumor cells with no or minimal damage to normal cells, with better safety and tolerability, and relatively less toxic side effects. However, traditional single-target drugs are not suitable for all lung cancer patients, precisely because targeted therapies are designed to attack specific target molecules, so the right target must be found in order to be effective. For most patients with non-small cell lung cancer, only the presence of EGFR mutation in the gene can form the “target” for targeted drug attack. The results of the TRIBUTE large randomized controlled study showed that the survival time of patients with KRAS mutation was significantly shorter, suggesting that KRAS mutation is an unfavorable factor affecting the efficacy of TKI drugs. Therefore, identifying the mutation sites of KRAS and EGFR genes in both primary and metastatic tumor foci is crucial for the selection of drug therapy targets.  When using targeted therapy, the possible inconsistency of gene mutation sites in primary and metastatic foci should not be ignored. Prior to targeted therapy, it is recommended that tumor tissue biopsies be performed on NSCLC patients to detect gene mutations in their primary and metastatic foci, so as to better select patients suitable for targeted therapy. The mutation sites of KRAS and EGFR genes in the primary and metastatic foci of NSCLC patients are not consistent, which means that for NSCLC patients who have developed metastasis, determining the status of these two genes in the primary and metastatic foci is an important reference for the selection of targeted therapy. In addition ROS1 gene fusion targeted drug clinical has achieved exciting study results, and in March 2016, FDA approved crizotinib (Pfizer) for the treatment of ROS1 positive metastatic NSCLC, bringing new options for the treatment of NSCLC. The recently published 2017 edition of the NCCN guidelines even included ROS1 gene fusion testing in the first-line treatment regimen for advanced NSCLC for the first time.  As a major means of individualized medicine, targeted therapy is a genetically or molecularly selected therapy that kills malignant tumor cells with little effect on normal cells, and is characterized by “high efficiency and low toxicity”. As a kind of in vitro diagnostic technology associated with targeted drugs, “concomitant diagnosis” mainly detects the expression level of proteins and mutated genes in human body to screen out the best drug users among different types of disease population for targeted individualized medical treatment. With the close collaboration of expertise and technology between diagnostic and pharmaceutical fields, “concomitant diagnosis” and targeted therapy have become the two most important tools to achieve precision medicine.  EGFR, ALK, and ROS1 (EAR) are important targets for lung cancer targeted therapy, and simultaneous EAR gene testing has been adopted by European ESMO as an effective strategy for patients to benefit from lung cancer precision medicine. Currently, there are many technologies applied to tumor genotyping, including real-time fluorescence quantitative PCR (RT-PCR), high-throughput sequencing, digital PCR (ddPCR), gene chips, fluorescence in situ hybridization (FISH) and so on. The high-throughput detection technologies that can be used for simultaneous detection of EAR genes mainly include sequencing, gene chip, RT-PCR, etc.  From the perspective of practical clinical application, more than ten lung cancer-related driver genes have been identified, and new targets are constantly being discovered. It is believed that with the discovery of new lung cancer targets and the development of new targeted drugs, the technology of high-throughput detection of more targets will be more beneficial to the formulation of precision medical decisions for lung cancer. We expect that high-throughput sequencing technology can solve the problems related to clinical application, and regulatory agencies can promote the standardization and standardization of clinical application of LDTs through policy reform. At the same time, we expect more and more institutions to develop assays that can detect more targets simultaneously through technological innovation and on a technology platform suitable for clinical application, so as to assist clinical planning for optimal treatment and save precious time for patients.