Project Details
Projekt
The role of non-coding RNAs in metastasis and therapy escape
Subject Area
Pathology
Term
from 2014 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 242727105
In recent years, several regimes of low-dose metronomic therapy (LDM) have been successful in cancer therapy especially for patients refractory to standard high-dose chemotherapy, for advanced stage disease and in maintenance therapy following high dose and targeted treatments. So far, known mechanisms of metronomic therapy include suppression of tumor-angiogenesis, stimulation of anticancer cytotoxic T-cell immune responses, inhibition of the hypoxia inducible factor-1 alpha (HIF-1), direct tumor cell targeting effects and the induction of tumor dormancy. Despite this, little is known about the molecular basis of LDM, e.g. the role of regulatory RNAs such as microRNAs (miRNAs), circular RNAs and long non-coding RNAs during LDM therapy. The general goal of our project is to characterize non-coding RNAs in primary tumors and metastasis during LDM therapy. During the first funding period, we have performed non-coding RNA screening and data analysis and started to characterize highly promising non-coding RNAs on a molecular level. The focus of our efforts in the next funding period is on further functional characterization as well as on non-coding RNA-based adaptation effects and therapy escape during LDM therapy. We will continue to use the BalbNeuT mouse model of breast cancer (central mouse project), the xenograft HT29.hCG.Luc SCID and the syngeneic CMT93.hCG.Luc C57BL/6 models of colon cancer. One of the ultimate goals of our endeavor is to find and manipulate a non-coding RNA and identify beneficial effects for LDM therapy.
DFG Programme
Research Units
