[Inhibiting the pro-tumor and transcription factor FACT: Mechanisms].
Conventional antitumor therapy is often complicated by the emergence of the so-called cancer stem cells (CSCs), which are characterized by low metabolic rates and high resistance to almost all existing therapies. Many problems of clinical oncology and a poor efficacy of current treatments in particular are ascribed to CSCs. Therefore, it is important to develop new compounds capable of eliminating both rapidly proliferating tumor cells and standard treatment-resistant CSCs. Curaxins have been demonstrated to manifest various types of antitumor activity. Curaxins simultaneously affect at least three key molecular cascades involved in tumor development, including the p53, NF-κB, and HSF1 metabolic pathways. In addition, studies of some curaxins indicate that they can inhibit the transcriptional induction of the genes for matrix metalloproteinases 1 and 8 (MMP1 and MMP8); the PI3K/AKT/mTOR signaling cascades; cIAP-1 (apoptosis protein 1) inhibitor activity; topoisomerase II; and a number of oncogenes, such as c-MYC and others. In vivo experiments have shown that the CSC population increases on gemcitabine monotherapy and is reduced on treatment with curaxin CBL0137. The data support the prospective use of FACT inhibitors as new anticancer drugs with multiple effects on cell metabolism.
Biological Faculty, Moscow State University, Moscow, 119234 Russia.|mal_nat@mail.ru.
N V
NV
Maluchenko
Fox Chase Cancer Center, Philadelphia, PA, 19111-2497, USA.
H W
HW
Chang
Fox Chase Cancer Center, Philadelphia, PA, 19111-2497, USA.
M T
MT
Kozinova
Biological Faculty, Moscow State University, Moscow, 119234 Russia.
M E
ME
Valieva
Biological Faculty, Moscow State University, Moscow, 119234 Russia.|Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
N S
NS
Gerasimova
Biological Faculty, Moscow State University, Moscow, 119234 Russia.
A V
AV
Kitashov
Biological Faculty, Moscow State University, Moscow, 119234 Russia.
M P
MP
Kirpichnikov
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
P G
PG
Georgiev
Biological Faculty, Moscow State University, Moscow, 119234 Russia.|Fox Chase Cancer Center, Philadelphia, PA, 19111-2497, USA.|Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.|vasily.studitsky@fccc.edu.
V M
VM
Studitsky
CBL0137; FACT; NF-κB and HSF1; SPT16; SSRP1; cancer stem cells; curaxins; p53