Significance of the response of quiescent cell populations within solid tumors in cancer therapy

Abstract

In analyzing the response of quiescent (Q) cells in solid tumors, we have developed a combined method with a micronucleus (MN) assay and the identification of proliferating (P) cells by 5-bromo-2'-deoxyuridine (BrdU) and an anti-BrdU monoclonal antibody. Using this method, the responses of Q tumor cells as well as total tumor (P+Q) cells within murine solid tumors to various DNA-damaging treatments were evaluated. Based on this evaluation, combining with tirapazamine, a well-known bioreductive agent, and/or heat treatment at mild temperatures was thought to be a promising modality for cancer therapy in terms of conventional anticancer treatment-resistant Q cell control. Recently, our method for detecting the Q-cell response using P cell labeling with BrdU and the MN frequency assay was also shown to be applicable to an apoptosis detection assay. Meanwhile, our method for detecting the intratumor Q-cell response was also applicable toward high linear energy transfer radiation, including reactor neutrons. Thus, using our method, a new neutron capture compound that has the potential to be distributed in neutron capture therapy-resistant intratumor Q cell populations is now under development.