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Session: ePoster: Basic and Translational Science 1 (Sun8)

EP208 - Topical Saquinavir Prevents Anal Cancer Development Via PI3K Inhibition

Sunday, May 11, 2025
8:49 AM – 8:54 AM PT
Location: Monitor 1, Sails Pavilion, Upper Level

    ePoster Presenter(s)

  • Corinne Praska, MD

    General Surgery Resident
    University of Wisconsin - Madison
    Madison, WI, United States

    All of the relevant financial relationships listed below have been mitigated.
    This individual has no financial relationships with ineligible companies.

    • Author(s)

  • EY

    Evan Yao, B.S.

    Laboratory Technician
    University of Wisconsin-Madison
    Madison, Wisconsin, United States

    Disclosure information not submitted.

  • SH

    Sakura Haggerty, n/a

    Undergraduate Researcher
    UW Madison undergraduate student
    Madison, Wisconsin, United States

    Disclosure information not submitted.

  • YZ

    YUN ZHOU, n/a

    Research Specialist
    UW-MADISON
    Middleton, Wisconsin, United States

    Disclosure information not submitted.

    • Senior Author(s)

  • EC

    Evie Carchman, MD, FACS

    Associate Professor
    University of Wisconsin School of Medicine and Public Health
    Madison, Wisconsin, United States

    All of the relevant financial relationships listed below have been mitigated.
    This individual has no financial relationships with ineligible companies.

All of the relevant financial relationships listed below have been mitigated.
Corinne Praska, MD: This individual has no financial relationships with ineligible companies.
Evie Carchman, MD, FACS: This individual has no financial relationships with ineligible companies.
Image or Table (Do Not add text here):

Purpose/Background: It has previously been shown that the topical protease inhibitor, saquinavir (SQV), can prevent cancer development in a transgenic mouse model of anal dysplasia. It has also been previously demonstrated that PI3K/mTOR inhibition can prevent cancer in this same mouse model. We hypothesized that SQV acts via PI3K and/or mTOR inhibition to prevent anal cancer development.

Methods/Interventions: Transgenic K14E6/E7 mice that spontaneously develop high-grade anal dysplasia at 25 weeks of age were generated. Thirty mice per group, with equal numbers of males and females, at 25 weeks of age were treated with or without topical SQV and with or without topical DMBA (to ensure cancer development). Mice were treated for 20 weeks. Anal samples from these mice were analyzed using immunohistochemistry for pS6 and pAKT to evaluate for effects on mTOR and PI3K, respectively.

Results/Outcomes: There was a statistically significant decrease in pAKT expression in mice treated with SQV alone compared to untreated control mice (Figure 1). There was a trend, albeit not statically significant, in mice treated with SQV in the setting of DMBA exposure compared to DMBA alone. There was no statistically significant difference between groups with regards to pS6 quantification.

Conclusion/Discussion: One mechanism through which topical SQV exerts its anal cancer preventative effects in vivo is via inhibition of PI3K, as noted by decreased pAKT expression.