Krebswissenschaft und -therapie

Purpose: In the case of developing resistance to systemic neoadjuvant chemotherapy, patients might tend to present with more advanced diseases later on and become inoperable at the end of their course. We have tried to determine the predictive factors for complete pathological response.

Materials and Methods: Records of 115 patients were reviewed retrospectively. We have collected data related to patient’s sociodemographic features, disease free survival and overall survival, as well as the clinical, histological, molecular and pathological features of their tumor. We have used SPSS statistic program (SPSS 20.0, SPSS Inc. Chicago, Illinois) to analyze statistical inputs.

Findings: 26 patients (22.6%) showed pathological Miller Payne Grade 5 response (T0) and 3 patients showed no measurable tumor, residue with separate tumor cells (T1mi). Presence of HER2-neu expression (p: 0.03), absence of ER and PR expression (p=0.001) and high histological grade (p: 0.025) were found to be associated with complete pathological response. Tumor diameter and lymphoid infiltration were not correlated with complete response. Also, we found that, patients who showed lower pathological nodal stage according to AJCC 8th system, have statistically significant longer survival times (p<0.05 for all), but Miller-Payne Grade 5 response were not predict survival results (p: 0.814 for OS) (p=0.295 for PFS).

Conclusion: Neoadjuvant treatment would be more effective in these types of tumors. Survival effect can be better predicted with pathologic nodal results according to AJCC 8th system. There is a need for randomized prospective studies so that the treatment response can be assessed more appropriately.

Because of the emergence of drug-resistant tumor cells, successful treatments of human malignancies have been difficult to achieve in the clinic. In spite of various approaches to overcome multi drug resistance, it has remained challenging and elusive. It is, therefore, necessary to define and understand the mechanisms of drug-induced tumor cell killing for the future development of anticancer agents and for rationally designed combination chemotherapies. The clinically active antitumor drugs, topotecan, doxorubicin, etoposide, and procarbazine are currently used for the treatment of human tumors. Therefore, a great deal research has been carried to understand mechanisms of actions of these agents both in the laboratory and in the clinic. These drugs are also extensively metabolized in tumor cells to various reactive species and generate oxygen free radical species (ROS) that initiate lipid peroxidation and induce DNA damage. However, the roles of ROS in the mechanism of cytotoxicity remain unappreciated in the clinic. In addition to ROS, various reactive nitrogen species (RNS) are also formed in tumor cells and in vivo. However, the importance of RNS in cancer treatment is not clear and has remained poorly defined. This review discusses the current understanding of the formation and the significance of ROS and RNS in the mechanisms of various clinically active anticancer drugs.