Because tumor necrosis factor-alfa (TNF) has been identified as possessing tumor-promoting properties in multiple malignant tumors, anti-TNF therapies have been proposed as a potential combination treatment that could enhance the effects of chemotherapy in patients with colon cancer.
Colon cancer is one of the most frequently diagnosed types of cancer and is subject to one of the highest mortality rates of any malignant disease. While some chemotherapy regimens can suppress progression slightly, the response rate to these treatments is low.
Because tumor necrosis factor-alfa (TNF) has been identified as possessing tumor-promoting properties in multiple malignant tumors, anti-TNF therapies have been proposed as a potential combination treatment that could enhance the effects of chemotherapy in patients with colon cancer.
In order to investigate this theory, a recently published study assessed the combination of the anti-TNF agent infliximab and oxaliplatin in colon cancer in an animal model.
The researchers collected colon cancer tissue samples from 60 patients who received oxaliplatin treatment after surgery, and the samples were evaluated for TNF levels. The researchers found that patients who were sensitive to oxaliplatin had lower mean TNF levels than patients whose disease was resistant to the therapy, a finding which suggests that TNF expression may alter the effect of chemotherapy. The investigators say that TNF may promote the resistance of colon cancer cells to oxaliplatin by inhibiting an immune response to tumor cells.
A mouse model was established using an oxaliplatin-resistant colon cancer cell line (CT-26-R); 1 week after the mice (n = 30) were inoculated with the cells, they were randomly assigned to 3 groups: the first received oxaliplatin (4 mg/kg) once per week, the second received oxaliplatin plus infliximab (4 mg/kg and 6 mg/kg, respectively) once per week, and the third received saline once per week. Tumor growth and survival were observed and recorded.
The group of mice receiving oxaliplatin plus infliximab exhibited the longest survival time (P <.0001). Furthermore, the tumor volume increase in the mice receiving the combination treatment was apparently inhibited compared with the mice receiving oxaliplatin alone (P =.001).
The researchers concluded that the combination of infliximab and oxaliplatin may increase the sensitivity of colon cancer cells to chemotherapy, and that anti-TNF therapy may enhance the efficacy of chemotherapy for patients with colon cancer.
Reference
Huang D, Xue J, Li S, Yang D. Oxaliplatin and infliximab synergize to induce regression of colon cancer.Oncol Lett. 2018;15(2):1517-1522. doi 10.3892/ol.2017.7468.
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