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Editorial
. 2012 Feb;21(2):135-8.
doi: 10.1517/13543784.2012.642369. Epub 2012 Jan 4.

Rapalogs in viral cancers

Dirk P Dittmer, Aadra P Bhatt, Blossom Damania
Editorial

Rapalogs in viral cancers

Dirk P Dittmer et al. Expert Opin Investig Drugs. 2012 Feb.

Abstract

At present, 150 clinical trials are registered with the National Cancer Institute, which investigate the efficacy of inhibitors of the PI3K/Akt/mTOR pathway against multiple cancers. Efficacy varies not so much with drug action, but with tumor type, as different cancer types (and different pre-clinical models) exhibit widely differing susceptibilities to mTOR inhibitors, such as rapamycin. Viral cancers appear to be among the most mTOR-addicted and most rapamycin-sensitive cancers. We discuss the different mTOR inhibitors that are currently available and in clinical trials. We also speculate how the molecular makeup of viral cancers could guide the selection and use of known and novel mTOR inhibitors to treat virus-associated malignancies.

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Conflict of interest statement

Declaration of interest

The authors have no other competing interests to declare. The authors state no conflict of interest and have received no payment in preparation of this manuscript.

Figures

Figure 1
Figure 1. Model of rapamycin modes of action in transplantation (left) and cancer (right)
If used as immune suppressants in solid organ transplantation, both rapamycin and FK506 inhibit translation of essential cytokines for activated T cells (IL-2). Rapamycin also inhibits the translation of essential cytokines for activated B cells (IL-6). If used as anti-cancer drugs for viral cancers, both rapamycin and FK506 inhibit IL-2 in herpesvirus saimiri (HVS)-induced T cell lymphoma (TL). Rapamycin also inhibits IL-6 in KSHV-induced primary effusion lymphoma (PEL). Eventually, clones of TL and PEL evolve, which no longer depend on IL-6 or in which IL-6 expression is rapamycin insensitive [3].
Figure 2
Figure 2. Current NCI registered clinical trials using inhibitors of the PI3K/Akt/mTOR pathway
(A). Stacked bar chart showing the number of trials (on the vertical axis) for different cancer categories (on the horizontal axis). The class of inhibitor is indicated by color. NHL, non-Hodgkin lymphoma; HCC, any liver cancer including hepatocellular carcinoma; HNC, head and neck cancer; Hem, hematopoietic malignancies including multicentric Castleman disease and leukemia; endome., endometrial cancer; HD, Hodgkin disease. (B) Stacked bar chart showing the number of trials (on the vertical axis) for different mTOR inhibitors (on the horizontal axis) grouped by mechanism of action. The phase of the trial is indicated by color.
See this image and copyright information in PMC

References

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