Objective  To reveal the current status of pharmacogenomics studies on colorectal cancer targeted monoclonal drugs and their adverse reactions, explore their development trend, and provide reference for later related studies.

Methods  Taking the core collection of Web of Science as the data source, combined with the visualization function of CiteSpace software, bibliometrics was used to analyze the authors, research institutions, publication countries, cited literatures, published journals, and keywords of targeted and monoclonal anti-colorectal cancer drugs in the aspects of genomics and adverse reactions from 2012 to 2022.

Results  After screening, 5 893 literatures in the past decade were included. There are 4 509 literatures related to genomics. The United States, Japan, Italy and China are the core countries in this field, holding the vast majority of core researches. There were 1 384 literatures related to adverse reactions, and the average number of papers published by authors was low and relatively independent, forming a small group of authors led by high-yield authors. Key words: biomarkers, molecular subtypes, anti-tumor combined chemotherapy, pharmacogenomic biomarkers for colorectal cancer target drugs, drug therapeutic targets, adverse reactions, prognosis, etc. By highlighting biomarkers of targeted therapeutic agents, the prognosis of advanced or metastatic treatment options for colorectal cancer can be evaluated. At the same time, we can search for special diagnostic targets related to the metabolism of targeted therapeutic drugs and find their biomarkers, which will become a hot research spot in the future.

Conclusions  To provide reference for researchers to accurately grasp the research status and development trend of anti-colorectal cancer targeting and monoclonal drugs.

1.Yuan Z, Weng S, Ye C, et al. CSCO guidelines for colorectal cancer version 2022: updates and discussions[J]. Chin J Cancer Res, 2022, 34(2): 67-70. DOI: 10.21147/j.issn.1000-9604.2022.02.01.

2.周川人, 姚菲, 黄晓颖, 等. 自噬促进结直肠癌细胞对5-氟尿嘧啶及顺铂的化疗耐药[J]. 华中科技大学学报（医学版）, 2021, 50(4): 434-439. [Zhou CR, Yao F, Huang XY, et al. Autophagy promotes chemotherapy resistance of colorectal cancer cells to 5-fluorouracil and cisplatin[J]. Journal of Huazhong University of Science and Technology (Medical), 2021, 50(4): 434-439.] DOI: 10.3870/j.issn.1672-0741.2021.04.005.

3.Garcia-Foncillas J, Sunakawa Y, Aderka D, et al. Distinguishing features of cetuximab and panitumumab in colorectal cancer and other solid tumors[J]. Front Oncol, 2019, 9: 849. DOI: 10.3389/fonc.2019.00849.

4.Ketzer S, Schimmel K, Koopman M, et al. Clinical pharmacokinetics and pharmacodynamics of the epidermal growth factor receptor inhibitor panitumumab in the treatment of colorectal cancer[J]. Clin Pharmacokinet, 2018, 57(4): 455-473. DOI: 10.1007/s40262-017-0590-9.

5.Fakih M, Vincent M. Adverse events associated with anti-EGFR therapies for the treatment of metastatic colorectal cancer[J]. Curr Oncol, 2010, 17(Suppl 1): S18-30. DOI: 10.3747/co.v17is1.615.

6.文磊, 张红梅, 徐立. 贝伐珠单抗在结直肠癌治疗中的应用[J]. 中国肿瘤, 2016, 25(7): 534-541. [Wen L, Zhang HM, Xu L. Application of bevacizumab in the treatment of colorectal cancer[J]. Chinese Tumor, 2016, 25(7): 534-541.] DOI: 10.11735/j.issn.1004-0242.2016.07.A008.

7.Kokol P, Blazun Vosner H, Zavrsnik J. Application of bibliometrics in medicine: a historical bibliometrics analysis[J]. Health Info Libr J, 2021, 38(2): 125-138. DOI: 10.1111/hir.12295.

8.陈悦, 陈超美, 刘则渊, 等. CiteSpace知识图谱的方法论功能[J]. 科学学研究, 2015, 33(2): 242-253. [Chen Y, Chen CM, Liu ZY, et al. The methodology feature of CiteSpace knowledge graph[J]. Scientific Research, 2015, 33(2): 242-253.] DOI: 10.3969/j.issn.1003-2053.2015.02.009.

9.Heinemann V, von Weikersthal LF, Decker T，et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2014, 15(10): 1065-1075. DOI: 10.1016/S1470-2045(14)70330-4.

10.Douillard JY, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer[J]. N Engl J Med, 2013，369(11): 1023-1034. DOI: 10.1056/NEJMoa1305275.

11.Grothey A, van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial[J]. Lancet, 2013, 381(9863): 303-312. DOI: 10.1016/S0140-6736(12)61900-X.

12.Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study[J]. Lancet Oncol, 2017, 18(9): 1182-1191. DOI: 10.1016/S1470-2045(17)30422-9.

13.Le DT, Uram JN, Wang H, et al. PD-1 Blockade in tumors with mismatch-repair deficiency[J]. N Engl J Med, 2015, 372(26): 2509-2520. DOI: 10.1056/NEJMoa1500596.

14.Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer[J]. Ann Oncol, 2016，27(8): 1386-1422. DOI: 10.1093/annonc/mdw235.

15.Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study[J]. J Clin Oncol, 2010, 28(31): 4697-4705. DOI: 10.1200/JCO.2009.27.4860.

16.Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer[J]. N Engl J Med, 2009, 360(14): 1408-1417. DOI: 10.1056/NEJMoa0805019.

17.Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma[J]. N Engl J Med, 2015, 373(19): 1803-1813. DOI: 10.1056/NEJMoa1510665.

18.Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer[J]. N Engl J Med, 2016, 375(19): 1823-1833. DOI: 10.1056/NEJMoa1606774.

19.Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J (Engl), 2022, 135(5): 584-590. DOI: 10.1097/CM9.0000000000002108.

20.Cao Y. VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs[J]. Nat Rev Endocrinol, 2014,  10(9): 530-539. DOI: 10.1038/nrendo.2014.114.