Synergy between an IGF-1R antibody and Raf/MEK/ERK and PI3K/Akt/mTOR pathway inhibitors in suppressing IGF-1R-mediated growth in hematopoietic cells

Bertrand, F. E.; Steelman, Linda S.; Chappell, William H.; Abrams, Stephen L.; Shelton, John G.; White, Edmond R.; Ludwig, Dale L.; McCubrey, James A.

doi:10.1038/sj.leu.2404217

Cited by 72 publications

(75 citation statements)

References 19 publications

(32 reference statements)

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“…IGF-1R has been reported to relieve leukemic cells of cytokine dependency. 28,29 IGF-1R activity is also implicated in several solid tumors, such as breast, prostate and colon, in which aberrant Hox gene expression has also been reported. [38][39][40] IGF-1R has been reported to be regulated by the c-Myb transcription factor.…”

Section: Hoxa9 Induced Expression Of Igf-1rmentioning

confidence: 99%

“…[25][26][27] IGF-1R has been reported to relieve leukemic cells of cytokine dependency. 28 However, BLIN-3 cells lack expression of endogenous HoxA9 14 and have retained an absolute requirement for growth factor/ stromal cell contact for optimal growth and proliferation. 15 IGF-1R protein expression was observed in the cytokine and stromal cell-independent cell lines SEMK2 and RS4;11 ( Figure 4d).…”

Section: Hoxa9 Activation Induces Surface Expression Of Igf-1rmentioning

confidence: 99%

“…32,35 IGF-1R expression has been reported in AML blasts and IGF-1 is capable of stimulating AML cell proliferation. 28,29,36,37 Several studies have indicated that inhibition of IGF-1R signaling results in a reduction of cell proliferation and induction of apoptosis, particularly in AML. 28,29,37 Our data indicate that one mechanism of Hox-mediated cell proliferation is through expression and subsequent activation of the IGF-1R receptor.…”

Section: Hoxa9 Induced Expression Of Igf-1rmentioning

confidence: 99%

“…28,29,36,37 Several studies have indicated that inhibition of IGF-1R signaling results in a reduction of cell proliferation and induction of apoptosis, particularly in AML. 28,29,37 Our data indicate that one mechanism of Hox-mediated cell proliferation is through expression and subsequent activation of the IGF-1R receptor. IGF-1R has been reported to relieve leukemic cells of cytokine dependency.…”

Section: Hoxa9 Induced Expression Of Igf-1rmentioning

confidence: 99%

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HoxA9 induces insulin-like growth factor-1 receptor expression in B-lineage acute lymphoblastic leukemia

Whelan

Ludwig²,

Bertrand

2008

Leukemia

Self Cite

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Section: Hoxa9 Induced Expression Of Igf-1rmentioning

confidence: 99%

Section: Hoxa9 Activation Induces Surface Expression Of Igf-1rmentioning

confidence: 99%

Section: Hoxa9 Induced Expression Of Igf-1rmentioning

confidence: 99%

Section: Hoxa9 Induced Expression Of Igf-1rmentioning

confidence: 99%

See 2 more Smart Citations

HoxA9 induces insulin-like growth factor-1 receptor expression in B-lineage acute lymphoblastic leukemia

Whelan

Ludwig²,

Bertrand

2008

Leukemia

Self Cite

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“…The mechanisms by which IGF1R inhibition fails to abrogate ERK activity in HCC cells remain unclear. It has been shown that A12, a monoclonal antibody against IGF1R, failed to inhibit ERK in leukemic cells treated with interleukin‐3 38. Therefore, it is possible that ERK can be activated by other upstream factors, such as interleukin‐3, and that IGF1R is not a major regulator of ERK activation in HCC cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of insulin‐like growth factor 1 receptor enhances the efficacy of sorafenib in inhibiting hepatocellular carcinoma cell growth and survival

Wang

Bank

Malnassy

et al. 2018

Hepatology Communications

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Hepatocellular carcinoma (HCC) is the fifth most common primary cancer and second largest cause of cancer‐related death worldwide. The first‐line oral chemotherapeutic agent sorafenib only increases survival in patients with advanced HCC by less than 3 months. Most patients with advanced HCC have shown limited response rates and survival benefits with sorafenib. Although sorafenib is an inhibitor of multiple kinases, including serine/threonine‐protein kinase c‐Raf, serine/threonine‐protein kinase B‐Raf, vascular endothelial growth factor receptor (VEGFR)‐1, VEGFR‐2, VEGFR‐3, and platelet‐derived growth factor receptor β, HCC cells are able to escape from sorafenib treatment using other pathways that the drug insufficiently inhibits. The aim of this study was to identify and target survival and proliferation pathways that enable HCC to escape the antitumor activity of sorafenib. We found that insulin‐like growth factor 1 receptor (IGF1R) remains activated in HCC cells treated with sorafenib. Knockdown of IGF1R sensitizes HCC cells to sorafenib treatment and decreases protein kinase B (AKT) activation. Overexpression of constitutively activated AKT reverses the effect of knockdown of IGF1R in sensitizing HCC cells to treatment with sorafenib. Further, we found that ceritinib, a drug approved by the U.S. Food and Drug Administration for treatment of non‐small cell lung cancer, effectively inhibits the IGF1R/AKT pathway and enhances the inhibitory efficacy of sorafenib in human HCC cell growth and survival in vitro, in a xenograft mouse model and in the c‐Met/β‐catenin‐driven HCC mouse model. Conclusion: Our study provides a biochemical basis for evaluation of a new combination treatment that includes IGF1R inhibitors, such as ceritinib and sorafenib, in patients with HCC. (Hepatology Communications 2018;2:732‐746)

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Molecular‐targeted agents combination therapy for cancer: Developments and potentials

Zhao

Wang

2013

Intl Journal of Cancer

120

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Although chemotherapy has advanced into the era of targeted drugs, the antitumor efficacies of current therapies are limited, most likely because of the high degree of cancer clonal heterogeneity, intratumor genetic heterogeneity and cell signal complexity. As shutdown of a single target does not necessarily eradicate the cancer, the use of combinations of molecular-targeted agents (MATs) has been proposed, and some pioneering research has been conducted to examine the efficacy of this strategy. In this article, the clinical and preclinical studies that are underway in an attempt to improve the anticancer efficacy of chemotherapies through combination strategies are summarized. Studies of combining cytotoxic agents with MATs, coinhibiting two or more targets in a single pathway or coinhibiting parallel or compensatory pathways as well as specific combinations will be introduced, and the antitumor potentials of each combination strategy will be evaluated.

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Synergy between an IGF-1R antibody and Raf/MEK/ERK and PI3K/Akt/mTOR pathway inhibitors in suppressing IGF-1R-mediated growth in hematopoietic cells

Cited by 72 publications

References 19 publications

HoxA9 induces insulin-like growth factor-1 receptor expression in B-lineage acute lymphoblastic leukemia

HoxA9 induces insulin-like growth factor-1 receptor expression in B-lineage acute lymphoblastic leukemia

Inhibition of insulin‐like growth factor 1 receptor enhances the efficacy of sorafenib in inhibiting hepatocellular carcinoma cell growth and survival

Molecular‐targeted agents combination therapy for cancer: Developments and potentials

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