Progress in targeted therapy of tumor KRAS gene mutation / 中国药理学通报

Targeting KRAS mutations has always been a difficult issue in clinical tumor therapy as most tumors are accompanied by KRAS gene mutations, which indicate poor prognosis. The mutant KRAS protein is difficult to design specific inhibitors in the conventional way of inhibiting the active sites, which is known as "undmggble" target. Therefore, the exploration of drug strategies targeting KRAS mutations has become a hot spot in the research and development of antitumor drugs. Although the research progress of targeted KRAS treatment strategy is limited, some new strategies that directly or indirectly inhibit mutant KRAS are still emerging in view of the deepening understanding of KRAS mutation function and malignant mechanism. In this review, we discussed the research progress of targeted therapy for KRAS gene mutation in tumor, hoping to provide the latest clues for the treatment of KRAS mutant tumor.

Effect of KRAS gene mutation and clinical factors on postoperative prognosis of rectal cancer patients / 实用医学杂志

Objective To investigate the effect of KRAS gene mutation and clinical factors on postopera-tive prognosis of rectal cancer patients and to explore their value in prognosis. Methods A total of 130 cases of rectal cancer patients from January to December 2010 were collected in the study. The tumor tissues sample was used to detect the KRAS gene mutation and 5-year follow-up was conducted. The correlation between KRAS gene mutation and clinical pathological features was analyzed.The clinic pathological factors that may affect the progno-sis were analyzed by survival analysis. Results Forty-five patients had mutations in No.2 expressed region of KRAS,with a mutation rate of 34.6%.KRAS gene mutation and stronger positive expression of EGFR(P<0.05), and multiple metastasis of tumor(P<0.05)were strongly coupled.The average survival of patients with wild-type KRAS gene was 57.5 months and that of patients with KRAS gene mutation 58.9 months but no significant differ-ence was observed(P>0.05).The TNM by high staging,multiple metastasis,lung metastasis and liver metasta-sis of cancer cells was closely related with poor postoperative prognosis of patients(P<0.05).The average surviv-al of postoperative patients in stage Ⅳ was 49months. Conclusions KRAS gene mutation in patients with rectal cancer after surgery is related with stronger positive expression of EGFR and multiple metastasis of cancer.TNM by high staging and metastatic sites affects the prognosis. The survival of rectal cancer after surgery in patients with stage Ⅳ are prolonged but the relation between KRAS genovariation and patients′ postoperative prognosis can not be determined.

Influence of primary resection and KRAS gene mutation in prognosis of mild symptomatic patients with stage Ⅳ colorectal cancer / 吉林大学学报(医学版)

Objective:To investigate the relationship between primary resection and KRAS gene mutation in the mild symptomatic patients with stage Ⅳ colorectal cancer,and to clarify its significance of prognosis.Methods:The clinical data of 46 mild symptomatic patients with stage Ⅳ colorectal cancer 2010 to December 2010 were collected.All the patients received primary resection.The KRAS gene mutation in the patients was detected by direct sequencing and the patients were followed up for 5 years.The influence of primary resection and KRAS gene mutation in prognosis of the patients with stage Ⅳ colorectal cancer was analyzed, and the clinical pathological features which might influence the prognosis were analyzed by survival analysis.Results:In 46 patients with colorectal cancer, KRAS gene mutation was found in 20 cases, the mutation rate was 43.4%, and most mutation was found at Codon 12. The KRAS mutation had relationship with the tumor site and multiple metastasis (P0.05).The median survival time of right colon cancer patients was 34.2 months, the median survival time of left colon cancer patients was 58.3 months, and there was sigificant difference (P<0.05).The cancer metastases including liver, lung and multiple metastasis were closely related to the poor prognosis of the colorectal cancer patients(P<0.05).The median survival time of the patients with stage Ⅳ colorectal cancer was 39.6 months after operation.Conclusion:After primary resection of the mild symptomatic patients with stage Ⅳ colorectal cancer,the median survival time of the patients with colorectal cancer in left colon site and right colon site were prolonged.Right colon cancer has more poorer prognosis than left colon cancer.KRAS gene mutation is associated with the tumor site and the multiple metastasis.The location of metastasis affect the prognosis.

Noonan Syndrome Confirmed to KRAS Gene Mutation: A Case of KRAS Gene Mutation

Noonan syndrome is an autosomal dominant disorder characterized by typical facial features, congenital heart disease, and short stature. Diagnosis is difficult only with clinical symptoms and it is recently confirmed with gene study. The genotype-phenotype correlations have been reported. We report a newborn with KRAS gene mutation. This is the second report of case with KRAS gene mutation in Korea. So we hope this case will be a help to diagnosis and treatment of Noonan syndrome from birth.