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Comment
. 2022 Aug;8(8):626-628.
doi: 10.1016/j.trecan.2022.06.004. Epub 2022 Jun 17.

Making a mouse out of a molehill: how precision modeling repurposes drugs for congenital giant nevi

Katerina Grafanaki  1 , Glenn Merlino  2 , Chi-Ping Day  3
Affiliations
Comment

Making a mouse out of a molehill: how precision modeling repurposes drugs for congenital giant nevi

Katerina Grafanaki et al. Trends Cancer. 2022 Aug.

Abstract

Patients with congenital giant nevi (CGN), which can compromise quality of life and progress to melanoma, have limited treatment options. Choi et al. have demonstrated that topical application of a proinflammatory hapten for alopecia treatment [squaric acid dibutylester (SADBE)] caused nevus regression and prevented melanoma in an Nras mouse CGN model. Their results demonstrate the promise of repurposing drugs through precision modeling.

Keywords: M1 macrophages; Nras; congenital giant nevi (CGN); drug repurposing; genetically engineered mice (GEM); squaric acid dibutylester (SADBE).

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Conflict of interest statement

Declaration of interests No interests are declared.

Figures

Figure 1.
Figure 1.. From human congenital nevi to murine congenital nevus models:
CGN as a single-driver disease was modeled in mice by inducing Nras expression in melanocytes of fetal/neonatal mice. Preclinical studies using the mouse model demonstrated that, SADBE, a hapten eliciting a contact hypersensitivity-like response, resulted in the recruitment of M1 macrophages, which could in turn elevate TNFα levels to cause cytotoxic activity, reducing melanocytes/nevocytes by apoptosis. SADBE treatment alone could also prevent melanomagenesis.
See this image and copyright information in PMC

Comment on

  • Topical therapy for regression and melanoma prevention of congenital giant nevi.
    Choi YS, Erlich TH, von Franque M, Rachmin I, Flesher JL, Schiferle EB, Zhang Y, Pereira da Silva M, Jiang A, Dobry AS, Su M, Germana S, Lacher S, Freund O, Feder E, Cortez JL, Ryu S, Babila Propp T, Samuels YL, Zakka LR, Azin M, Burd CE, Sharpless NE, Liu XS, Meyer C, Austen WG Jr, Bojovic B, Cetrulo CL Jr, Mihm MC, Hoon DS, Demehri S, Hawryluk EB, Fisher DE. Choi YS, et al. Cell. 2022 Jun 9;185(12):2071-2085.e12. doi: 10.1016/j.cell.2022.04.025. Epub 2022 May 12. Cell. 2022. PMID: 35561684 Free PMC article.

References

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Publication types

Supplementary concepts