OPPORTUNITIES FOR TARGET IDENTIFICATION TO PREVENT AND TREAT CANCER REGIMEN-RELATED TOXICITIES

Stephen Thomas Sonis

Brigham and Women's Hospital, Boston, Massachusetts, USA

Abstract

Toxicities represent collateral damage incurred by normal tissues following virtually every form of non-surgical cancer therapy and adversely impact patients’ ability to tolerate optimum treatment by unleashing a myriad of untoward symptoms. Regimen-related toxicities (RRT) result in specific tissue injury such as mucositis and dermatitis, as well as systemic pathoses like fatigue. RRTs also generate incremental costs that significantly add to the total costs of care. Three themes have emerged as being central to RRTs. First, they do not occur uniformly across tumor/treatment-specific cohorts; only a portion of patients develop clinically significant toxicities despite being treated in exactly the same way as patients who sail through therapy. Second, the pathogenesis of toxicities is complex consisting of a pathway sequence which almost always involves oxidative stress, innate immunity, and pro-inflammatory or inflammatory components. And third, germline genes markedly impact the risk and course of toxicities and response to attempts of their mitigation. Additionally, the patient’s microbiome and tumor-associated somatic mutations may impact RRTs. This presentation will discuss methods to prospectively define toxicity risk, differentiate patients who respond to preventive or interventional treatments from those who do not, and the pathobiologic characterization of toxicity etiology as a means to identify druggable targets for their prevention and treatment.

Keywords: Cancer, treatment, toxicities, genomics, inflammation.