The continuous development of high-throughput sequencing (NGS) technology and the significant reduction in sequencing costs have provided favorable conditions for the realization of precise and accurate treatment of tumor patients in clinical practice. Annoroad has earnestly selected 868 genes that are closely related to tumors, covering all the genes recommended by the guidelines and clinical hotspot genes, and analyzes the relationship between 268 drugs and gene variants, helps gene detection in lung cancer patients, especially for those with recurrence and metastasis at advanced stage.
According to different samples available from patients, Annoroad has developed two types of testing products:
1) High-throughput sequencing has good sensitivity, specificity and accuracy, as well as relatively high consistency between tissue samples and ctDNA liquid biopsy, and ctDNA test may serve as a supplement to tissue biopsy;
2) ctDNA test is non-invasive and allows real-time sampling, which can be used as a favorable tool for dynamic monitoring of recurrence and drug resistance;
3) ctDNA test can overcome the detection differences caused by tumor tissue heterogeneity;
4) High-throughput sequencing gene detection can discover new driver genes and promote the development of new drugs.Tumor histopathological typing is the essential foundation of current clinical antineoplastic protocols, but an increasing number of clinical studies have demonstrated that, molecular typing based on tumor driver gene mutations can help patients to select more targeted individualized treatment regimens, thus realizing precise and accurate treatment.
Figure source: Li et al. J Clin Oncol 31:1039-1049. 2013
| Gene | Associated Targeted Drugs |
| EGFR (guideline recommendation) | Erlotinib, Gefitinib, Icotinib, Afatinib, Osimertinib (AZD9291) |
| ALK (guideline recommendation) | Crizotinib, Erlotinib, Gefitinib, Icotinib, Ceritinib, Alectinib |
| ROS1 (guideline recommendation) | Crizotinib, Erlotinib, Gefitinib, Icotinib, Cabozantinib |
| BRAF (guideline recommendation) | Dabrafenib, Vemurafenib |
| MET (guideline recommendation) | Crizotinib, Erlotinib, Gefitinib, Icotinib, Ceritinib, Alectinib |
| RET (guideline recommendation) | Cabozantinib, Vandetanib |
| ERBB2/HER2 (guideline recommendation) | Afatinib, Trastuzumab |
| KRAS | Erlotinib, Gefitinib, Icotinib |
| TP53 | Possibly associated with poor prognosis |
Figure source: Shaw et al. New England Journal of Medicine. No1. Vol.374: 54-61.2016
This case is a milestone case of lung cancer managed under the guidance of NGS throughout the course of the disease, and it is also one of the very typical cases of precise and accurate medical treatment. Assisted by searching for gene variation information, clinical staged treatment regimens are adjusted, so that patients can obtain better quality of life.
Figure source: Shaw et al. New England Journal of Medicine. No1. Vol.374: 54-61.2016
In the treatment process of tumor patients, drug resistance often occurs, and tumor heterogeneity and tumor clonal evolution under drug pressure are often the root causes of drug resistance. Take the above figure as an example. The evolutionary tree in the figure represents the changes of tumor driver genes. Different drug-resistant gene mutations may concurrently occur in the lesions, such as TP53 site mutation, EGFR T790M drug-resistant mutation, c-Met amplification mutation, etc. This leads to temporal heterogeneity of tumors and induces drug resistance. In addition, the metastases at different sites may have different drug resistance mechanisms. With the development of high-throughput sequencing technology, it has become possible to conduct gene detection and find the molecular mechanism of drug resistance in patients by using this technology. Many patients can be managed in the whole treatment cycle through gene detection, just like typical patient cases do.
