Targeting the cancer initiating cell: The Achilles’ heel of cancer

McCubrey, James A.; Chappell, William H.; Abrams, Stephen L.; Franklin, Richard A.; Long, Jacquelyn M.; Sattler, Jennifer A.; Kempf, Christian; Laidler, Piotr; Steelman, Linda S.

doi:10.1016/j.advenzreg.2010.09.002

Cited by 13 publications

(10 citation statements)

References 63 publications

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“…Inappropriate activation of these pathways could result in the generation of drug resistant cells as well as cancer initiating cells (CICs). [60][61][62][63][64][65][66][67][68][69] In the following studies, the effects of Akt-1 activation on the response of breast cancer cells to chemotherapeutic-and hormonal-based drugs and radiation were examined as these three different approaches are used to treat breast cancer. Elevated Akt-1 expression resulted in resistance to doxorubicin, tamoxifen and radiation.…”

Section: Involvement Of Akt and Mtor In Chemotherapeutic And Hormonalmentioning

confidence: 99%

Involvement of Akt and mTOR in chemotherapeutic- and hormonal-based drug resistance and response to radiation in breast cancer cells

et al. 2011

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Section: Involvement Of Akt and Mtor In Chemotherapeutic And Hormonalmentioning

confidence: 99%

Involvement of Akt and mTOR in chemotherapeutic- and hormonal-based drug resistance and response to radiation in breast cancer cells

et al. 2011

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“…Only recently have researchers begun to assess the impact of soy isoflavones directly on CSCs. McCubrey et al [117] identified cancer initiating cells that have stem cell characteristics from PC-3 cell line by culturing these cells in media containing 25 nmol/L of the chemotherapeutic drug doxorubicin, a method that had been established and published earlier by the same research group [118]. They showed that while PC3 cells were highly sensitive to docetaxel compared with the PC3-derived cancer initiating cells, they did not display significant differences in the sensitivity to genistein which was able, at low physiologic doses, to reduce the IC50 of PC3-derived cancer initiating cells for docetaxel by approximately 200-fold.…”

Section: Introductionmentioning

confidence: 99%

Soy isoflavones and prostate cancer: A review of molecular mechanisms

Mahmoud

Yang

Bosland

2014

The Journal of Steroid Biochemistry and Molecular Biology

227

153

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Soy isoflavones are dietary components for which an association has been demonstrated with reduced risk of prostate cancer (PCa) in Asian populations. However, the exact mechanism by which these isoflavones may prevent the development or progression of PCa is not completely understood. There are a growing number of animal and in vitro studies that have attempted to elucidate these mechanisms. The predominant and most biologically active isoflavones in soy products, genistein, daidzein, equol, and glycetin, inhibit prostate carcinogenesis in some animal models. Cell-based studies show that soy isoflavones regulate genes that control cell cycle and apoptosis. In this review, we discuss the literature relevant to the molecular events that may account for the benefit of soy isoflavones in PCa prevention or treatment. These reports show that although soy isoflavone-induced growth arrest and apoptosis of PCa cells are plausible mechanisms, other chemo protective mechanisms are also worthy of consideration. These possible mechanisms include antioxidant defense, DNA repair, inhibition of angiogenesis and metastasis, potentiation of radio- and chemotherapeutic agents, and antagonism of estrogen- and androgen-mediated signaling pathways. Moreover, other cells in the cancer milieu, such as the fibroblastic stromal cells, endothelial cells, and immune cells, may be targeted by soy isoflavones, which may contribute to soy-mediated prostate cancer prevention. In this review, these mechanisms are discussed along with considerations about the doses and the preclinical models that have been used.

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“…These pathways also play key roles in the genesis of cancer initiating cells (CICs, a.k.a. cancer stem cells) [13-22]. …”

Section: Introductionmentioning

confidence: 99%

Involvement of Akt-1 and mTOR in Sensitivity of Breast Cancer to Targeted Therapy

et al. 2011

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Elucidating the response of breast cancer cells to chemotherapeutic and hormonal based drugs is clearly important as these are frequently used therapeutic approaches. A signaling pathway often involved in chemo- and hormonal-resistance is the Ras/PI3K/PTEN/Akt/mTOR cascade. In the studies presented in this report, we have examined the effects of constitutive activation of Akt on the sensitivity of MCF-7 breast cancer cells to chemotherapeutic- and hormonal-based drugs as well as mTOR inhibitors. MCF-7 cells which expressed a constitutively-activated Akt-1 gene [ΔAkt-1(CA)] were more resistant to doxorubicin, etoposide and 4-OH-tamoxifen (4HT) than cells lacking ΔAkt-1(CA). Cells which expressed ΔAkt-1(CA) were hypersensitive to the mTOR inhibitor rapamycin. Furthermore, rapamycin lowered the IC50s for doxorubicin, etoposide and 4HT in the cells which expressed ΔAkt-1(CA), demonstrating a potential improved method for treating certain breast cancers which have deregulated PI3K/PTEN/Akt/mTOR signaling. Understanding how breast cancers respond to chemo- and hormonal-based therapies and the mechanisms by which they can become drug resistant may enhance our ability to treat breast cancer. These results also document the potential importance of knowledge of the mutations present in certain cancers which may permit more effective therapies.

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Targeting the cancer initiating cell: The Achilles’ heel of cancer

Cited by 13 publications

References 63 publications

Involvement of Akt and mTOR in chemotherapeutic- and hormonal-based drug resistance and response to radiation in breast cancer cells

Involvement of Akt and mTOR in chemotherapeutic- and hormonal-based drug resistance and response to radiation in breast cancer cells

Soy isoflavones and prostate cancer: A review of molecular mechanisms

Involvement of Akt-1 and mTOR in Sensitivity of Breast Cancer to Targeted Therapy

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