Colorectal cancer is one of the most common malignancies. the incidence of colorectal cancer in China increased by 32.0% in urban areas and 8.5% in rural areas in the 1990s compared to the 1970s. Colorectal cancer has now become the most common malignancy affecting the health of Chinese people. However, the overall treatment effect of colorectal cancer is still unsatisfactory, and the 5-year survival rate still hovers around 60%. Recurrence and metastasis are the two major causes of death for colorectal cancer patients. Multi-modality comprehensive treatment has become the basic principle of colorectal malignant tumor treatment. At present, in addition to surgery (including minimally invasive treatment), chemotherapy and radiation therapy, molecular targeted therapy, interventional therapy, thermotherapy and biological therapy and many other therapies bring certain benefits to tumor patients. The most important factor affecting the survival of colorectal cancer patients is tumor stage; therefore, the application of adjuvant therapy (including chemotherapy and radiotherapy) in clinical practice is currently judged mainly according to TNM stage. However, there is no evidence so far that . These clinical indicators can predict the effectiveness of adjuvant chemotherapy for patients with colorectal cancer. There are some patients, even if they receive adjuvant chemotherapy, the survival benefit is not obvious; while there are also patients, even without adjuvant chemotherapy, have a better prognosis. In stage II colon cancer, 60% to 70% of patients can be cured by surgery, but 15% to 20% of patients still recur even after receiving chemotherapy. In stage III colon cancer, surgery can cure 40-50% of patients, but about 35% of patients will recur despite chemotherapy after surgery. For stage IV colon cancer, where distant metastases are present, patients are often treated with fluorouracil (5-FU), platinum-based drugs, or targeted agents, but it is not possible to predict which patients will be effective with these costly drugs. Only cetuximab can be predicted by Kras gene assay. Therefore, considering the adverse effects of adjuvant chemotherapy, the cost of treatment and the impact on patients’ quality of life, there are significant social and economic benefits of studying predictors of benefit from chemotherapy. Selecting appropriate treatment according to the specific conditions of colorectal cancer and formulating appropriate individualized treatment strategies for patients have become the main development direction of colorectal cancer treatment today, which is in line with the concept of personalized medicine. A perfect individualized treatment should be a precise treatment plan for patients based on clinical indicators including stage and molecular markers. Based on the current clinical experience and research evidence, the first step towards perfection is to make the initial screening and selection of patients and to administer the appropriate “quasi-individualized treatment” plan. This requires the following aspects. A standardized clinical pathway for colorectal cancer The standardized pathway includes early diagnosis, standardized surgical techniques and radiotherapy plans. Based on evidence-based medicine, clinicians should follow the basic principles of colorectal cancer treatment, synthesize the assessment results of biological characteristics of tumor, pathological stage and prognosis correlation, and provide the best treatment for colorectal cancer patients in accordance with the medical level at that time after multidisciplinary discussion. Early diagnosis of colorectal cancer is a worldwide challenge. Medical history questioning, high-risk factor screening, family history tracing, fecal occult blood testing and colonoscopy screening are the main tools for traditional early diagnosis. However, the early diagnosis rate is still low due to invasive nature and poor population compliance. The percentage of early colorectal cancer (T1-4aN0M0) in the United States is 39%. Less than 15% in China. Fecal DNA testing and virtual colonoscopy are emerging screening tools, but further clinical validation and economic analysis are still needed for widespread clinical implementation. The introduction of the concept of total mesorectal excision (TME) in 2009 has standardized rectal cancer surgery worldwide. More than 20 years later, the concept of complete mesocolic excision (CME) was also introduced. The introduction of these concepts has led to increasing standardization of surgical practices in colorectal cancer, a significant reduction in interoperator variability, and greater comparability between clinical studies, and will reduce a major confounding factor in studies related to individualized treatment. Current chemotherapeutic agents for colorectal cancer include 5-FU, platinum oxalate, topoisomerase I inhibitors (irinotecan), and targeted agents such as vascular endothelial growth factor (VEGF) receptor blockers (bevacizumab) and epithelial growth factor (EGF) receptor blockers (erbitux). Currently, chemotherapy for colorectal cancer suffers from inadequate treatment cycles and arbitrary regimens (drugs, doses, and regimens), and the indications for targeted drugs are not standardized, and there is the phenomenon of overtreatment. Due to the lack of convincing clinical research evidence, a significant proportion of colorectal cancer patients in China have inadequate chemotherapy cycles and sometimes discontinue chemotherapy or change the frequency of treatment arbitrarily: moreover, the dose, duration and delivery mode of radiotherapy are highly heterogeneous among different hospitals, and even quite arbitrary in some places. Such a situation poses considerable difficulties in assessing the effectiveness of chemotherapy and comparing the advantages and disadvantages of different regimens. If radiotherapy regimens are not standardized, the research of individualized treatment will be difficult. The observation endpoint of colorectal cancer treatment is mainly recurrence and death. Combining the basic clinical data, blood specimen test results, pathological specimen examination and analysis results with the observation endpoints can form the basic elements of individualized treatment research. All research requires data, and comprehensive and accurate collection of relevant data is the most basic requirement for research. The establishment of standardized clinical data database, tumor tissue specimen repository and gene library can only lay the foundation for the detection and research of histological typing, cell typing, genotyping and gene mutation of colorectal tumors, provide strong support for the establishment of postoperative individualized treatment and prognosis prediction model, and meet the demand for basic and clinical research on colorectal tumors. Tissue libraries can be used to establish a molecular screening system for new drug candidates based on tumor specimens. The establishment of tissue microarray technology and evaluation of candidate drug targets, the establishment of high-throughput detection technology of biomarkers and individualized drug use of new drugs. Only through follow-up can we obtain information on patient recurrence or death. Follow-up examinations for colorectal cancer usually include anal finger examination, sigmoidoscopy, fecal occult blood test, carcinoembryonic antigen (CEA), CT and MRI, and patients may or may not have obvious symptoms at the time of examination. Most of the local recurrences of rectal cancer are located outside the intestinal cavity, and the significance of anamnesis, endoscopy and fecal occult blood tests is not significant at this time. Most of the local recurrence occurs within 2 years after surgery, with 6-12 months after surgery as the peak recurrence period. Very few appear after 5 years of surgery. More importantly, the degree and extent of local recurrence varies widely among patients due to early and late detection. Close follow-up for at least 2 years after rectal cancer has been recommended, and a Meta-analysis by Renehan et al. showed that intensive follow-up could significantly advance the diagnosis of recurrence by 8.5 months and reduce the morbidity and mortality rate of rectal cancer patients by 9% to 13%. However, it is still unclear as to which follow-up means is most effective. III. Accelerated research of molecular markers The research process of molecular markers can be roughly divided into: (1) discovery of molecular markers; (2) clinical correlation study; (3) clinical prospective validation; and (4) clinical application. There are many aspects of the research process, especially the clinical evaluation phase. For example, in the case of clinical relevance studies. Since a large number of molecular markers (at the gene level, RNA level and protein level) have been identified in previous studies, it would be labor-intensive to conduct clinical correlation studies on each of these molecular markers. Therefore, at the early stage of research, molecular markers with strong clinical relevance can be initially selected for further clinical relevance studies and clinical validation by reading a lot of literature and based on the impact factor of journals, citation frequency of articles, etc. With the development of experimental technology, high-throughput analysis is now widely used in tumor research. Techniques such as Genome-wide Association (GWA) and single nucleotide polymorphism (SNP) are becoming less and less costly. In fact, the actual clinical economics of these studies will ultimately yield benefits that far outweigh the cost of these studies. Corresponding statistical theories and statistical software have emerged to handle the enormous amount of information generated by these experimental techniques, to analyze their correlation with the prognosis of tumor patients, and to make judgments about the effectiveness and prognosis of chemotherapy. In clinical trials, it is quite difficult to validate experimental results prospectively, and several guidelines have been developed to help in this regard. One of the more well-documented molecular markers in the prediction of colorectal cancer outcome, especially in II colon cancer, is microsatellite instability (MSI). DNA microsatellites are repetitive sequences of short nucleotides that are abundant in the human genome. Abnormal shortening or lengthening of microsatellites leads to MSI and thus cancer, often due to functional defects in mismatch repair genes (including MLH1, MSH2, MSH6, and PMS2). Defects in mismatch repair genes are seen in 80% of Lynch syndrome and also in 15%-20% of patients with sporadic colon cancer who have this mutation. Under normal conditions, the mismatch repair system recognizes the complex created by DNA binding to 5-FU, which activates the cascade amplification of apoptosis, while defective mismatch repair loses this function, resulting in MSI. more convincing data on MSI have been presented in the PETACC-3 study: patients with stage II and III colon cancer with high microsatellite instability (MSI-H), their disease-free survival and overall survival. had better disease-free survival and overall survival than microsatellite stable (MSS) and microsatellite low instability (MSI-L). This disparity in prognosis was particularly evident in stage II colon cancer. Overall, patients with MSI are often clinically staged earlier, have a better prognosis, are mostly seen in the right hemicolectomy, and respond poorly to 5-FU chemotherapy. Another molecular marker that has been widely used in clinical practice is K-ras gene status. Currently, the NCCN guidelines as well as the “Colorectal Cancer Diagnostic and Treatment Standards (2010 Edition)” issued by the Ministry of Health of China] have recommended that K-ras gene status should be routinely tested prior to cetuximab treatment, and K-ras gene testing alone can eliminate about 40% of patients with K-ras gene mutations that are not effective against the drug. The cost of K-ras gene testing is less than $1,000, while the cost of targeted drugs is close to $100,000. B-raf genetic testing is gradually being added to the routine testing program. In addition to these single molecular markers, the Oncotype DX Colon Cancer Assay and the ColoPrint Assay are combinations of two molecular markers that contain tests for 12 and 18 genes, respectively. The former has been validated in a sample of 1436 patients with stage II colon cancer, and the predicted recurrence risk coefficients calculated after testing with 12 genes were significantly correlated with prognosis, with recurrence rates of 9% to 1 1% for low recurrence coefficients and 25% to 27% for high recurrence coefficients. However, none of these so-called combinations or models have been prospectively clinically validated. And they were only used to predict recurrence and were not used to directly predict the effectiveness of chemotherapy. Others such as AKT, JNK, MET, IGF1R, MAPK, Notch and circulating tumor cells are still under investigation; APC, PIK3CA, SMAD4 and TP53 are associated with chromosomal instability (CIN) and their relevance to the prognosis of colorectal cancer is also under investigation. Future prospects Individualized treatment is the inevitable direction of colorectal cancer diagnosis and treatment development. There is no doubt that there is a long way to go for perfect individualized treatment. Therefore, the accuracy and precision of data as well as the integrity and reliability of tissue specimens are fundamental to the study of individualized treatment. The initial screening of molecular markers or their combination to form a suite of tests and their validation in the clinic. Ultimately, the task of obtaining meaningful molecular markers is a daunting one. However, we have entered the era of individualized treatment for colorectal cancer. The road to individualized treatment may be bumpy, but in the end, we will give the best individualized treatment based on the recognition of the uniqueness of each tumor to achieve the rational integration of medical resources and the maximization of patient outcomes.