Effect of Neoadjuvant Chemoradiation Therapy on Proteasome Pool in Rectal Cancer

Abstract

In untreated rectal cancer patients, the chymotrypsin-like activity of proteasomes in tumor tissue was 3-fold higher than that in conventionally normal tissue, which is explained by up-regulation of expression of immunoproteasomes and total pool of proteasomes. After neoadjuvant chemoradiation therapy, expressions of the total pool of proteasomes and immunoproteasomes in the tumor as well as the relative ratios of these indices to those in conventionally normal tissue were smaller by 1.4-3.3 times in comparison with the untreated patients. These changes were paralleled with pronounced (4.5-fold) down-regulation of proteasome activity in the tumor and a 3.7-fold decrease of activity ratio for the proteasomes in tumor and in conventionally normal tissue. The number of immunoproteasome subunits and the chymotrypsin-like activity of proteasomes can be viewed as potential markers to prognosticate effectiveness of neoadjuvant chemoradiation therapy in rectal cancer patients.

<p>Definitive radiotherapy or chemoradiotherapy for distal rectal cancer with early stage of cT1-2N0</p>

“…Chemoradiation therapy suppresses the expression of immune subunits in the tumor and thereby downregulates proteasomal CTLA. Thus, the expression of immune subunits and proteasomal CTLA may serve as potential markers to predict the effectiveness of neoadjuvant chemoradiation in patients with rectal cancer 20. In another study performed by Rau et al, results showed that patients with decreased p21 expression following chemoradiotherapy achieved better disease-free survival ( p =0.03) and patients with increased proliferative activity, as measured by increased post-therapy Ki-67 expression, also had better disease-free survival ( p <0.005).…”