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Surgical Debulking Modifies Notch Signaling and May Improve Vismodegib Effectiveness for Locally Advanced Basal Cell
Natella Maglakelidze1, Samantha L Gettle1, Amy L Longenecker1
1Department of Dermatology, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Summary
Surgical debulking before vismodegib treatment for locally advanced basal cell carcinoma (LaBCC) may alter tumor molecular pathways. This approach showed clinical responses in some patients, suggesting potential for improved outcomes in LaBCC treatment.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- Vismodegib is effective for locally advanced basal cell carcinoma (LaBCC), but side effects limit its use.
- Surgical debulking prior to vismodegib has shown promise for prolonged remission in LaBCC.
- Understanding molecular changes post-debulking is crucial for optimizing LaBCC therapy.
Purpose of the Study:
- To assess clinical outcomes of LaBCC patients treated with debulking followed by vismodegib.
- To analyze molecular changes in LaBCC tissue after surgical debulking.
Main Methods:
- Four LaBCC patients underwent debulking surgery followed by vismodegib.
- Punch biopsies of residual tumor tissue were collected one week post-debulking.
- RT-qPCR, immunoblot, and immunostaining analyzed Notch and Wnt signaling pathways.
Main Results:
- Elevated expression of PTCH1, HEY2, LGR6, FZD2, LEF1, ALCAM, and RUNX1 genes was observed post-debulking.
- Notch signaling was confirmed to be elevated in follow-up biopsies.
- Three out of four patients showed a clinical response to the combined therapy.
Conclusions:
- Surgical manipulation of LaBCC correlates with molecular pathway alterations.
- This combination therapy may offer a viable treatment strategy for LaBCC.
- Further research is needed to elucidate the mechanisms of cellular reprogramming induced by surgery.
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