Thalidomide and lenalidomide: Mechanism-based potential drug combinations

@article{Vallet2008ThalidomideAL,
  title={Thalidomide and lenalidomide: Mechanism-based potential drug combinations},
  author={Sonia Vallet and Antonio Palumbo and Noopur S. Raje and Mario Boccadoro and Kenneth C. Anderson},
  journal={Leukemia \& Lymphoma},
  year={2008},
  volume={49},
  pages={1238 - 1245}
}
Thalidomide and its analogue lenalidomide are potent anti-inflammatory, anti-angiogenic and immunomodulatory drugs, successfully used for the treatment of hematological cancers, in particular multiple myeloma (MM). Both drugs reveal a dual mechanism of action: they target tumour cells by direct cytotoxicity and, indirectly, by interfering with several components of the bone marrow microenvironment. Lenalidomide and thalidomide are versatile drugs with a broad range of activities that potentiate… 

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References

SHOWING 1-10 OF 84 REFERENCES

Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy.

Clinical activity of Thal against MM that is refractory to conventional therapy is demonstrated and mechanisms of anti-tumor activity of thalidomide and its potent analogs (immunomodulatory drugs [IMiDs]) are delineated.

The evolution of thalidomide and its IMiD derivatives as anticancer agents

A series of immunomodulatory drugs — created by chemical modification of thalidomide — have been developed to overcome the original devastating side effects, and their powerful anticancer properties mean that these drugs are now emerging from thalidmide's shadow as useful anticancer agents.

Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma.

In vitro and in vivo data support the hypothesis that Thal may mediate its anti-MM effect, at least in part, by modulating NK cell number and function.

Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo

The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density.

Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects

This study assessed the anti-angiogenic activity of compounds from both IMiD™ and SelCID™ classes of analogues using a novel in vitro multicellular human assay system and the established rat aorta assay.

Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for myeloma patients

A retrospective analysis to assess the efficacy and toxicity profile when lenalidomide was used in combination with cyclophosphamide and dexamethasone for patients with relapsed refractory disease found the side effect profile of the combination was highly tolerable.

Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications.

The mechanism of action of IMiDs against MM cells in vitro is delineated and form the basis for clinical trials of these agents, alone and coupled with conventional and other novel therapies, to improve outcome in MM.

Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma.

  • S. ScheyP. Fields A. Dalgleish
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2004
This is the first report demonstrating in vivo T-cell costimulation by this class of compound, supporting a potential role for CC-4047 as an immunostimulatory adjuvant treatment.

Antitumor activity of thalidomide in refractory multiple myeloma.

Thalidomide can induce marked and durable responses in some patients with multiple myeloma, including those who relapse after high-dose chemotherapy, and is active against advancedMyeloma.

Thalidomide--a revival story.

The recent return of thalidomide stems from the broad spectrum of its pharmacologic and immunologic effects.
...