Reprogramming the Metastatic Microenvironment to Combat Disease Recurrence
Abstract
This research aims to eliminate the mortality associated with metastatic breast cancer. We will do so by: 1) testing a novel combination of clinically available therapeutic agents that modulate the metastatic tumor microenvironment for the prevention of metastatic disease and 2) using existing breast cancer patient samples to create a biomarker panel that combines disseminated tumor cell (DTC)classification and immune-subtyping to identify those patients most likely to benefit from this new treatment approach. In spite of recent advances in patient stratification and the use of targeted adjuvant therapies, 10- 20 of patients with invasive tumors will eventually develop metastatic disease 1, 2. These data indicate that for a significant percentage of patients, adjuvant therapies are ineffective at eliminating DTCs, which give rise to life threatening metastatic lesions. Therefore, the development of new clinical approaches that are effective at preventing metastatic breast cancer (BC) is of paramount importance. One promising approach is to reprogram the tissue microenvironments that provide safe harbor for DTCs during adjuvant therapy. Bone is one such metastatic safe harbor. Sixty-seven percent of metastatic patients will develop disease in the bone, which has been proposed to be a reservoir of malignant cells destined for subsequent metastatic relapse in the bone and visceral organs. Interactions between DTCs and the bone microenvironment lead to pathological bone loss, which can stimulate tumor cell outgrowth. In addition to contributing to morbidity, this vicious cycle also protects tumor cells from the cytotoxic effects of chemotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2016
- Accession Number
- AD1032096
Entities
People
- David Denardo
Organizations
- University of Washington