Table 3. Preclinical studies in primary effusion lymphoma other than proteasome inhibition.
| Study | Agent | Activity | Model | Key findings |
|---|---|---|---|---|
| Targeting PI3-kinase pathway | ||||
| Hussain et al.53 | Bay11-7085 ±LY294002 | NF-κB±PI3-K inhibition | In vitro: PEL cell lines | Synergistic apoptotic responses in PEL cells |
| Uddin et al.65 | LY294002 | PI3-kinase inhibition | In vitro: PEL cell lines | Apoptosis in all PEL cell lines studied except BCP1 |
| Targeting mTOR pathway | ||||
| Gasperini et al.67 | Rapamycin (sirolimus) | mTOR inhibition | In vitro: PEL cell lines; in vivo: xenograft mouse model | No eradication of PEL; after an initial response, development of resistance in PEL cells treated with rapamycin |
| Sin et al.58 | Rapamycin (sirolimus) | mTOR inhibition | In vitro: PEL cell lines; in vivo: xenograft mouse model | Inhibition of PEL growth in culture; delay of PEL progression in vivo |
| Targeting STAT3 pathway | ||||
| Aoki et al.66 | Dominant-negative STAT3 vector; tyrphostin AG490 | STAT3 inhibition Jak2 inhibition | In vitro: PEL cell lines | Induction of apoptosis and decrease of survivin expression in PEL after inhibition of STAT3 signaling |
| Antiviral±IFN-α | ||||
| Fujimuro et al.70 | Gancyclovir (purine nucleoside analogs) | Antiviral activity | In vitro: PEL cell lines | Cytotoxic activity toward KSHV-infected PEL cells treated with gancyclovir but not with acyclovir |
| Wu et al.51 | AZT and IFN-α | Antiviral activity | In vivo: xenograft mouse model | Increased survival of PEL mice |
| Lee et al.59 | AZT and IFN-α | Antiviral activity | In vitro: PEL cell lines | Minimal sensitivity to AZT alone but synergy with IFN-α |
| Miscellaneous | ||||
| Goto et al.71 | Zoledronic acid | Induction of Vg9Vd2 T cells | In vitro: PEL cell lines; in vivo: xenograft mouse model | Inhibition of growth of PEL cells and improved survival of PEL mice |
| Paul et al.72 | Nimesulide | COX-2 inhibitor | In vitro: PEL cell lines | Proliferation arrest |
| Bhatt et al.68 | Brentuximab vedotin | Anti-CD30 monoclonal and drug conjugate | In vitro: PEL cell lines; in vivo: xenograft mouse model | Proliferation arrest in PEL cell lines; prolonged survival in PEL mice |
| Lan et al.73 | Gamma-secretase inhibitor (GSI) | Intracellular activated Notch1 (ICN) blockage | In vivo: direct xenograft model | Delay of the onset of tumorigenesis of treated PEL mice |
Abbreviations: AZT, azidothymidine; HDAC, histone deacetylase; IFN-α, interferon-alpha; KSVH, Kaposi sarcoma-associated herpesvirus; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor kappa B; PEL, primary effusion lymphoma; PI3-K, phosphoinositide-3-kinase; STAT3, signal transducer and activator of transcription 3.