Abstract
Rectal cancer represents approximately 10% of cancers worldwide. Preoperative chemoradiotherapy increases complete pathologic response and local control, although it offers a poor advantage in survivorship and sphincter saving compared with that of radiotherapy alone. After preoperative chemoradiotherapy, approximately 20% of patients with rectal cancer achieve a pathologic complete response to the removed surgical specimen; this response may be related to a better prognosis and an improvement in disease-free survival. However, better biomarkers to predict response and new targets are needed to stratify patients and obtain better response rates.MAP17 (PDZK1IP1) is a small, 17 kDa non-glycosylated membrane protein located in the plasma membrane and Golgi apparatus and is overexpressed in a wide variety of human carcinomas. MAP17 has been proposed as a predictive biomarker for reactive oxygen species, ROS, inducing treatments in cervical tumors or laryngeal carcinoma. Due to the increase in ROS, MAP17 is also associated with the marker of DNA damage, phosphoH2AX (pH2AX). In the present manuscript, we examined the values of MAP17 and pH2AX as surrogate biomarkers of the response in rectal tumors. MAP17 expression after preoperative chemoradiotherapy is able to predict the response to chemoradiotherapy, similar to the increase in pH2AX. Furthermore, we explored whether we can identify molecular targeted therapies that could help improve the response of these tumors to radiotherapy. In this sense, we found that the inhibition of DNA damage with olaparib increased the response to radio- and chemotherapy, specifically in tumors with high levels of pH2AX and MAP17.
Highlights
Rectal cancer represents approximately 10% of cancers worldwide [1]
Preoperative chemoradiotherapy increases complete pathologic response and local control, it offers a poor advantage in survivorship and sphincter saving compared with that of radiotherapy alone
We explored whether we can identify molecular targeted therapies that could help improve the response of these tumors to radiotherapy
Summary
Rectal cancer represents approximately 10% of cancers worldwide [1]. In 2012, there were 446.801 newly diagnosed cases and 214.727 deaths attributed to this entity in Europe [1]. The standard of care in patients with locally advanced rectal cancer is preoperative chemoradiotherapy before surgical excision. The addition of preoperative radiation therapy improves local control and survival in this set of patients [3,4,5,6,7,8]. Preoperative chemoradiotherapy increases the complete pathologic response and local control, it offers a poor advantage in survivorship www.oncotarget.com and sphincter saving compared with that of radiotherapy alone [9,10,11,12,13]. Approximately 20% of patients with rectal cancer achieve a pathologic complete response in the surgical specimen removed, which may be related with a better prognosis and an improvement in disease-free survival [14]. Better biomarkers to predict response and new targets are needed to stratify patients and to obtain better response rates
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