NT157 exhibits antineoplastic effects by targeting IRS and STAT3/5 signaling in multiple myeloma

de Queiroz, Gustavo Nery; Lima, Keli; de Miranda, Livia Bassani Lins; Rego, Eduardo Magalhães; Traina, Fabiola; Machado-Neto, João Agostinho

doi:10.1016/j.htct.2024.02.017

Cited by 1 publication

(2 citation statements)

References 37 publications

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“…These collective effects limit tumor cell access to the vasculature, thereby impeding metastasis [40]. Notably, NT157 retains its efficacy in inducing programmed cell death mechanisms such as apoptosis and autophagy [49,54]. Moreover, by modulating the tumor microenvironment, NT157 mitigates tumor-promoting inflammation [38,40].…”

Section: Discussionmentioning

confidence: 99%

“…In hematological malignancies, including acute lymphoblastic leukemia [50], myeloproliferative neoplasm [33,51], chronic myeloid leukemia [52,53], and multiple myeloma [54], NT157 also demonstrated remarkable antineoplastic effects. Notably, NT157 exhibited efficacy even in chronic myeloid leukemia models harboring the BCR::ABL1 T315I mutation [52], which confers resistance or partial resistance to most currently employed clinically tyrosine kinase inhibitors [55].…”

Section: Impact Of Nt157 On Cellular Processes In Experimental Cancer...mentioning

confidence: 99%

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NT157 as an Anticancer Drug Candidate That Targets Kinase- and Phosphatase-Mediated Signaling

Lima,

Machado-Neto

2024

Kinases and Phosphatases

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Cancer, characterized by uncontrolled cell growth and metastasis, represents a significant challenge to public health. The IGF1/IGF1R axis plays a pivotal role in tumor proliferation and survival, presenting an attractive target for intervention. NT157, a small molecule tyrphostin, has emerged as a promising inhibitor of this axis, displaying potent antineoplastic effects across various cancer types. This review synthesizes the literature on NT157’s mechanism of action and its impact on cellular processes in experimental cancer models. Initially identified for inducing the serine phosphorylation of IRS1 and IRS2, leading to their degradation and inhibiting the IGF1R signaling cascade, subsequent studies revealed additional targets of NT157, including STAT3, STAT5, and AXL, suggesting a multifaceted mechanism. Experimental evidence demonstrates that NT157 effectively suppresses tumor growth, metastasis, and angiogenesis in diverse cancer models. Additionally, NT157 enhances chemotherapy efficacy in combination therapy. Moreover, NT157 impacts not only tumor cells but also the tumor microenvironment, modulating inflammation and immune responses by targeting cancer-associated fibroblasts, myeloid cells, and immune cells, creating a suppressive milieu hindering tumor progression and metastasis. In conclusion, NT157 exhibits remarkable versatility in targeting multiple oncogenic pathways and hallmarks of cancer, underscoring its potential as a promising therapeutic agent.

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Section: Discussionmentioning

confidence: 99%

Section: Impact Of Nt157 On Cellular Processes In Experimental Cancer...mentioning

confidence: 99%

NT157 as an Anticancer Drug Candidate That Targets Kinase- and Phosphatase-Mediated Signaling

Lima,

Machado-Neto

2024

Kinases and Phosphatases

Self Cite

View full text Add to dashboard Cite

show abstract

NT157 exhibits antineoplastic effects by targeting IRS and STAT3/5 signaling in multiple myeloma

Cited by 1 publication

References 37 publications

NT157 as an Anticancer Drug Candidate That Targets Kinase- and Phosphatase-Mediated Signaling

NT157 as an Anticancer Drug Candidate That Targets Kinase- and Phosphatase-Mediated Signaling

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