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Chemical Compound Review:

Afinitor

Synonyms: Certican, Zortress, Votubia, Everolimus, everolimusum, ...

Roccaro, A.M. et al., Johnson, B.E. et al., Mabuchi, S. et al., Marinov, M. et al., Daver, N. et al.

Bruce E. Johnson, David Jackman, Pasi A. Jänne,

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Disease relevance of Certican

These results indicate that RAD001 could have therapeutic efficacy in human ovarian cancers with hyperactivated AKT/mTOR signaling [1].
Importantly, everolimus targeted Waldenstrom macroglobulinemia cells even in the context of bone marrow milieu, where it affected migration, adhesion, and angiogenesis [2].
The combination of HyperCVAD and everolimus is well tolerated and moderately effective in relapsed ALL, specifically T-ALL [3].

Associations of Certican with other chemical compounds

This manuscript will review the preclinical rationale for undertaking a study of erlotinib combined with everolimus for patients with relapsed NSCLC [4].
In the sensitive cells, RAD001 showed a strong additive effect to the proapoptotic action of the chemotherapeutic agent etoposide [5].

References

RAD001 inhibits human ovarian cancer cell proliferation, enhances cisplatin-induced apoptosis, and prolongs survival in an ovarian cancer model. Mabuchi, S., Altomare, D.A., Cheung, M., Zhang, L., Poulikakos, P.I., Hensley, H.H., Schilder, R.J., Ozols, R.F., Testa, J.R. Clin. Cancer Res. (2007) [Pubmed]
Mechanisms of activity of the TORC1 inhibitor everolimus in Waldenstrom macroglobulinemia. Roccaro, A.M., Sacco, A., Jia, X., Banwait, R., Maiso, P., Azab, F., Flores, L., Manier, S., Azab, A.K., Ghobrial, I.M. Clin. Cancer Res. (2012) [Pubmed]
A Phase I/II Study of the mTOR Inhibitor Everolimus in Combination with HyperCVAD Chemotherapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia. Daver, N., Boumber, Y., Kantarjian, H., Ravandi, F., Cortes, J., Rytting, M.E., Kawedia, J.D., Basnett, J., Culotta, K.S., Zeng, Z., Lu, H., Richie, M.A., Garris, R., Xiao, L., Liu, W., Baggerly, K.A., Jabbour, E., O'Brien, S., Burger, J., Bendall, L.J., Thomas, D., Konopleva, M. Clin. Cancer Res. (2015) [Pubmed]
Rationale for a phase I trial of erlotinib and the mammalian target of rapamycin inhibitor everolimus (RAD001) for patients with relapsed non small cell lung cancer. Johnson, B.E., Jackman, D., Jänne, P.A. Clin. Cancer Res. (2007) [Pubmed]
AKT/mTOR pathway activation and BCL-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001. Marinov, M., Ziogas, A., Pardo, O.E., Tan, L.T., Dhillon, T., Mauri, F.A., Lane, H.A., Lemoine, N.R., Zangemeister-Wittke, U., Seckl, M.J., Arcaro, A. Clin. Cancer Res. (2009) [Pubmed]

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