Antisheddaasi strategia esim ADAM10/ADAM17 inhibiittorit ?

Cancer Biol Ther. 2016 Aug; 17(8): 870–880.

Published online 2016 Apr 26. doi: 10.1080/15384047.2016.1177684

PMCID: PMC5004698

PMID: 27115328

The ADAMs family of proteases as targets for the treatment of cancer

Maeve Mullooly,^a,b Patricia M. McGowan,^b,c John Crown,^d and Michael J. Duffy^b,e

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004698/

Conclusion

Although several different ADAMs have been implicated in cancer development and evolution, the strongest evidence is found with ADAM17. Indeed, as mentioned above, there is substantial preclinical evidence supporting the involvement of this ADAM in cancer development or metastasis. These findings have encouraged the development of multiple inhibitors against ADAM17 for their potential use in the treatment of cancer. However, because of the multiplicity of actions mediated by ADAM17, it might be expected that long-term blockage of its protease activity would cause toxicity such as depressed immunity and an increased risk of infection. Such toxicity however, did not appear to emerge in the short-term animal model studies reported to date. Furthermore with the only ADAM10/17 inhibitor so far investigated in clinical trials, i.e., INCB7839 in phase I/II trials, no major toxicity was reported.^40,41 Indeed, INCB7839, in contrast to the early MMP inhibitors investigated for potential anti-cancer activity, did not cause musculoskeletal side effects.^35,36 To-date, monoclonal antibodies against ADAM17 do not appear to have undergone studies in clinical trials. These biological inhibitors however, might be expected to exhibit more specific targeting than low molecular weight compounds and thus have less toxicity. The time may now be ready to test ADAM17 monoclonal antibodies in clinical trials.