Pim is an oncogene that has anti-apoptotic functions and collaborates with the proto-oncogene Myc to cause tumor growth. ![]() The Pim family of kinases, including Pim-1, Pim-2, and Pim-3, promotes the inactivation of the pro-apoptotic protein Bad by phosphorylation. Establishing more effective, objective markers that identify patients who are unlikely to benefit from neoadjuvant treatment would have a great impact in clinical practice. All selection criteria used by doctors are based on pelvic magnetic resonance imaging (MRI) and ultrasound colonoscopy findings, such as invasion of all layers of the rectal wall and metastases to regional lymph nodes and the mesorectal fascia. Neoadjuvant treatment may delay the opportunity for radical surgical resection in approximately 30% of rectal cancer patients who would not benefit from chemoradiotherapy and may even lead to progression of the tumor or metastasis during treatment 3. Selection of the most suitable patients for chemoradiotherapy is difficult for oncologists. Therefore, neoadjuvant treatment for rectal cancer remains to be optimized. Previous studies on locally advanced rectal cancer patients five years after neoadjuvant treatment have reported 65.2–76% overall survival rates, 52.2–68% disease-free survival rates, 6–10.7% local recurrence rates, and 34.4–36% distant metastasis rates 6, 12, 13. However, the pathologic complete response (pCR) rate following neoadjuvant treatment is reported to be low at 10–20% 11. In most cases, a complete response or subtotal tumor regression after neoadjuvant treatment is associated with better patient outcomes 10. The Ryan grading system, which is based on the degree of post-neoadjuvant treatment regressive changes, including fibrosis, and the percentage of residual tumor, was recommended by the NCCN guideline and AJCC. The effects of neoadjuvant chemoradiotherapy have usually been determined by histopathologic investigation using tumor regression grading (TRG) systems, such as those by Mandard, Becker, Dworak, and Rodel 9. Over the past decade, the use of neoadjuvant chemoradiotherapy has dramatically increased in China. Based on these results, neoadjuvant chemoradiotherapy has been recommended by both the ESMO and NCCN guidelines 6, 7 to improve the prognosis of locally advanced or stages II and III resectable rectal cancer 8. Several randomized controlled clinical trials demonstrated that chemoradiotherapy could reduce the local recurrence rate of rectal cancer, reduce the tumor mass, and increase the tumor resection rate 5, 6. In patients with rectal cancer, especially the locally advanced type, the local recurrence rates even after radical resection are high and were reported to range from 15% to 16% 3 and to be associated with poor prognosis 3, 4. In China, the incidence of rectal cancer is higher than that of colon cancer 2. Pim-3 is a potential predictive biomarker for the response of rectal cancer to chemoradiotherapy.Ĭolorectal cancer is the fifth most commonly diagnosed cancer and fifth cause of cancer death in China in both men and women 1. ![]() Neoadjuvant chemotherapy cycles ( P = 0.007), adjuvant chemotherapy cycles ( P = 0.004) and pathology types ( P = 0.049) were significant prognostic factors for disease-free survival. Cox multivariate analysis showed that the significant prognostic factors were Pim-3 expression ( P = 0.003) and the number of neoadjuvant chemotherapy cycles ( P = 0.005) for overall survival. The patients with no Pim-3 expression were more likely to achieve a pathologic complete response to chemoradiotherapy than patients with Pim-3 expression ( P = 0.001). The relationship between Pim-3 expression on immunohistochemical analysis of rectal cancer tissue, which was obtained before treatment, the response to chemoradiotherapy and survival was investigated. 175 rectal cancer patients who underwent neoadjuvant treatment enrolled in this study. ![]() Therefore, the relationship between Pim-3 expression and response to neoadjuvant chemoradiotherapy in rectal cancer patients is important to evaluate. Pim-3 is a member of the provirus integration site for a moloney murine leukemia virus family of proteins that contributes to cell proliferation, survival, and chemotherapy resistance. Approximately 30% of locally advanced rectal cancer patients might not benefit from chemoradiotherapy however, the response to neoadjuvant chemoradiotherapy in these cases is difficult to predict.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |