TY - JOUR
T1 - The Influence of Mitochondrial Energy and 1C Metabolism on the Efficacy of Anticancer Drugs
T2 - Exploring Potential Mechanisms of Resistance
AU - Franczak, Marika
AU - Toenshoff, Isabel
AU - Jansen, Gerrit
AU - Smolenski, Ryszard T.
AU - Giovannetti, Elisa
AU - Peters, Godefridus J.
N1 - Funding Information: This study received grants from the National Science Centre of Poland (2018/31/B/NZ7/02909) (MF, GJP, RTS) and IDUB (Grant No. 664/256/62-0212) (GJP, RTS), AIRC IG-24444/MIUR 2018 and KWF Grant No. 11897 (EG). Publisher Copyright: © 2023 Bentham Science Publishers.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - Mitochondria are the main energy factory in living cells. To rapidly proliferate and metastasize, neoplastic cells increase their energy requirements. Thus, mitochondria become one of the most important organelles for them. Indeed, much research shows the interplay between cancer chemoresistance and altered mitochondrial function. In this re-view, we focus on the differences in energy metabolism between cancer and normal cells to better understand their resistance and how to develop drugs targeting energy metabolism and nucleotide synthesis. One of the differences between cancer and normal cells is the higher nicotinamide adenine dinucleotide (NAD+) level, a cofactor for the tricarbox-ylic acid cycle (TCA), which enhances their proliferation and helps cancer cells survive under hypoxic conditions. An important change is a metabolic switch called the Warburg effect. This effect is based on the change of energy harvesting from oxygen-dependent transformation to oxidative phosphorylation (OXPHOS), adapting them to the tumor en-vironment. Another mechanism is the high expression of one-carbon (1C) metabolism en-zymes. Again, this allows cancer cells to increase proliferation by producing precursors for the synthesis of nucleotides and amino acids. We reviewed drugs in clinical practice and development targeting NAD+, OXPHOS, and 1C metabolism. Combining novel drugs with conventional antineoplastic agents may prove to be a promising new way of anti-cancer treatment.
AB - Mitochondria are the main energy factory in living cells. To rapidly proliferate and metastasize, neoplastic cells increase their energy requirements. Thus, mitochondria become one of the most important organelles for them. Indeed, much research shows the interplay between cancer chemoresistance and altered mitochondrial function. In this re-view, we focus on the differences in energy metabolism between cancer and normal cells to better understand their resistance and how to develop drugs targeting energy metabolism and nucleotide synthesis. One of the differences between cancer and normal cells is the higher nicotinamide adenine dinucleotide (NAD+) level, a cofactor for the tricarbox-ylic acid cycle (TCA), which enhances their proliferation and helps cancer cells survive under hypoxic conditions. An important change is a metabolic switch called the Warburg effect. This effect is based on the change of energy harvesting from oxygen-dependent transformation to oxidative phosphorylation (OXPHOS), adapting them to the tumor en-vironment. Another mechanism is the high expression of one-carbon (1C) metabolism en-zymes. Again, this allows cancer cells to increase proliferation by producing precursors for the synthesis of nucleotides and amino acids. We reviewed drugs in clinical practice and development targeting NAD+, OXPHOS, and 1C metabolism. Combining novel drugs with conventional antineoplastic agents may prove to be a promising new way of anti-cancer treatment.
KW - 1C metabolism
KW - Cancer
KW - NAD
KW - mitochondria
KW - oxidative phosphorylation (OXPHOS)
KW - resistance
UR - http://www.scopus.com/inward/record.url?scp=85147421040&partnerID=8YFLogxK
U2 - https://doi.org/10.2174/0929867329666220401110418
DO - https://doi.org/10.2174/0929867329666220401110418
M3 - Review article
C2 - 35366764
SN - 0929-8673
VL - 30
SP - 1209
EP - 1231
JO - Current medicinal chemistry
JF - Current medicinal chemistry
IS - 11
ER -