Linking Serine/Glycine Metabolism to Radiotherapy Resistance
Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. 616, 6200 MD Maastricht, The Netherlands
Laboratory for Disease Mechanisms in Cancer, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Michael I. Koukourakis
Received: 5 February 2021
Revised: 5 March 2021
Accepted: 8 March 2021
Published: 10 March 2021
Hyperactivation of the de novo serine/glycine biosynthesis across different cancer types and its critical contribution in tumor initiation, progression, and therapy resistance indicate the relevance of serine/glycine metabolism-targeted therapies as therapeutic intervention in cancer. In this review, we specifically focus on the contribution of the de novo serine/glycine biosynthesis pathway to radioresistance. We provide a future perspective on how de novo serine/glycine biosynthesis inhibition and serine-free diets may improve the outcome of radiotherapy. Future research in this field is needed to better understand serine/glycine metabolic reprogramming of cancer cells in response to radiation and the influence of this pathway in the tumor microenvironment, which may provide the rationale for the optimal combination therapies.