Of interest, STAT5 seems to play an important role in the regulation of hematopoietic stem cell self-renewal suggesting that combination therapies including STAT5 inhibitors can erode the cancer stem cell pool and possibly open the way for the complete cancer eradication.
Signal transducer and activator of transcription 5 (STAT5) plays a key role in the malignancy of many tumors and has been identified as a therapeutic target.
Hyperactive STAT3 and STAT5 are also implicated in various hematopoietic and solid malignancies, such as chronic and acute myeloid leukemia, melanoma or prostate cancer.
Moreover, we showed that the epigenetic rebalance between decreased BCR-ABL/STAT5/c-Myc and enhanced STAT3/multi-drug resistance (MDR) pathways is characteristic of the cancer stem cell-like property of K562/ADR.
This study, along with other studies of constitutively active STAT mutants, provides insight into the pathogenesis and treatment of STAT5-driven cancer.
We identify a direct cooperation between STAT5 and HOXA9 at the transcriptional level and identify PIM1 kinase as a possible drug target in mutant JAK/STAT/HOXA9-positive leukemia cases.<i>Cancer Discov; 8(5); 616-31.
STAT5 is an important transcription factor that is constitutively activated in various types of malignancies, including chronic myelogenous leukemia (CML).
Hyperprolactinemia-inducing antipsychotics instigate precancerous cells to progress to cancer via JAK/STAT5 to suppress the apoptosis anticancer barrier, and these cancer-promoting effects can be prevented by prophylactic anti-JAK/STAT5 treatment.
STAT5 is aberrantly activated through phosphorylation in many types of cancer and this constitutive activation is associated with cell survival, proliferation, and self-renewal.
In summary, CM363 is a novel multikinase modulator that offers advantages to circumvent imanitib resistance and might be therapeutically effective in Bcrl-Abl-Stat5 related malignancies.
Cdc42, a target of miR-424, influences cancer stem cell activity by positively regulating prdm14 through activation of pak1 (p-21-activated kinase 1) and stat5.
STAT5 interacts with other factors to control transcription, and the mechanism of regulation is of interest as constitutive active STAT5 has been reported in malignancies.
Nevertheless, its roles in human cancer are still ambiguous, and its mechanisms are sophisticated as well, referring to a variety of targets and signal pathways, such as STAT5B, KRAS, MAPK/ERK signal pathway, Notch pathway, etc.
Abnormal activation of the γc cytokine JAK/STAT signaling pathway assessed by STAT3 or STAT5b phosphorylation was present in a proportion of many T-cell malignancies.
STAT5 is involved in many types of cancer, including chronic myelogenous leukemia (CML), in which this protein is found constitutively activated as a consequence of BCR-ABL expression.
The effects of Jak Stat signaling and the persistent activation of Stat3 and Stat5 on tumor cell survival, proliferation and invasion have made the Jak Stat pathway a favorite target for drug development and cancer therapy.
Signal transducers and activators of transcription 5 (STAT5) are known to be activated in a variety of malignancies and involved in tumor proliferation, apoptosis, and invasion, whereas the expression and biological role of STAT5b in PDAC are less clearly defined.
The cancer cell line encyclopedia and associated gene-expression data were used to correlate the activation status of STAT5 with the induction of a set of STAT5 target genes.
STAT3 and STAT5b mutations can be used as molecular markers for LGL leukemia diagnostics, and they present novel therapeutic targets for STAT3 and STAT5b inhibitors, which currently are in development for treatment of cancer and autoimmune disorders.