Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance

McCubrey, James A.; Steelman, Linda S.; Abrams, Steven L.; Lee, John Tayu; Chang, Fumin; Bertrand, F. E.; Navolanic, Patrick M.; Terrian, David M.; Franklin, Richard A.; D’Assoro, Antonio B.; Salisbury, Jeffrey L.; Mazzarino, María Clorinda; Stivala, Franca; Libra, Massimo

doi:10.1016/j.advenzreg.2006.01.004

Cited by 579 publications

(521 citation statements)

References 97 publications

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“…The fact that not all effectors of Ras mediate the same biological effects of Ras is consistent with previous studies that showed, for example, that the Raf/Mek pathway predominantly mediates proliferation whereas the PI3K/Akt drives survival. [27][28][29][30][31][32] Furthermore, our results are consistent with other reports that demonstrated that the RalGDS/RalA-RalB pathway downstream of Ras may be more important at mediating Ras-driven malignant transformation than the PI3K/Akt and the Raf-1/Mek pathways in some but not all tumors. 27 Interestingly, we have found that depletion of RalA and RalB in some tumors, particularly those of pancreatic origin, such as Panc-1 and MiaPacca-2 cells, does not result in decreasing survivin levels.…”

Section: Discussionsupporting

confidence: 92%

Depletion of K-Ras promotes proteasome degradation of survivin

Tecleab

Sebti²

2013

Cell Cycle

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Section: Discussionsupporting

confidence: 92%

Depletion of K-Ras promotes proteasome degradation of survivin

Tecleab

Sebti²

2013

Cell Cycle

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“…To enhance anticancer activity of sorafenib, the combination of sorafenib and doxorubicin was evaluated in several studies. Sorafenib plus doxorubicin is an attractive regimen since inhibition of Ras/Raf/MEK/ERK signaling pathway by sorafenib may suppress expression of MDR-1 (70). Therefore, the combination can increase area under the curve (AUC) of doxorubicin without worsening toxicities (71).…”

Section: Combination With Sorafenibmentioning

confidence: 99%

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

Kim

Talati

Kim

2017

J. Gastrointest. Oncol.

244

168

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Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis.The incidence of HCC and HCC-related deaths have increased over the last several decades. However, the treatment options for advanced HCC are very limited. Sorafenib remains the only drug approved for systemic treatment for advanced HCC. However, prior to sorafenib era conventional cytotoxic chemotherapies have been studied in advanced HCC. In this review, clinical studies of systemic chemotherapy for advanced HCC will be summarized and discussed.

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“…A complete loss of PTEN is more frequent in metastatic than in primary tumors 16 In vitro and clinical studies confirmed that deregulation of the PI3K/PTEN/Akt pathway was associated with resistance to doxorubicin and tamoxifen, drugs commonly used in metastatic breast cancer therapy. 18 This may have significant implications since chemotherapy and hormonal therapy are basic modalities for the treatment of metastatic breast carcinoma. On the other side, specific mutations we detected in our case, give new insights in both breast carcinogenesis and novel therapeutic modalities.…”

Section: Discussionmentioning

confidence: 99%