Sendurai Mani, Associate Director of Translational Oncology at Legorreta Cancer Center, shared on LinkedIn:
“Top 200 most influential cancer papers – Paper 57: PTCH1 – linking Hedgehog signaling to cancer
I recently shared an AI – generated (Claude) list of the top 200 papers that have shaped cancer research on LinkedIn.
Today, I share more about Paper 57.
What if a developmental signaling pathway normally used to build tissues becomes reactivated in cancer?
In 1996, Hahn and colleagues published a landmark Cell paper identifying mutations in the human homolog of patched (PTCH) in nevoid basal cell carcinoma syndrome.
This inherited syndrome is associated with multiple basal cell carcinomas and other developmental abnormalities.
PTCH1 is a key regulator of the Hedgehog signaling pathway, a pathway essential during embryonic development.
Normally, PTCH1 restrains Hedgehog signaling.
When PTCH1 function is lost:
PTCH1 loss – Hedgehog pathway activation – abnormal proliferation – tumor formation
The discovery established PTCH1 as a tumor suppressor and directly linked developmental signaling to cancer biology.
This had broad implications.
Cancer cells can reactivate pathways that are normally tightly controlled during development, using them to promote growth and survival.
The work also paved the way for targeted therapies aimed at Hedgehog signaling, including SMO inhibitors used in selected patients with advanced basal cell carcinoma.
The scientific progression is powerful:
Inherited cancer syndrome – PTCH1 mutation – Hedgehog pathway activation – cancer dependency – targeted inhibition.
The enduring lesson: Pathways that guide normal development can become dangerous when their regulation is lost in adult tissues.
Hahn H, Wicking C, Zaphiropoulos PG, et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 1996;85:841–851.
DOI.”
Title: Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome
Authors: Heidi Hahn, Carol Wicking, Peter G Zaphiropoulos, Mae R Gailani, Susan Shanley, Abirami Chidambaram, Igor Vorechovsky, Erika Holmberg, Anne Birgitte Unden, Susan Gillies, Kylie Negus, Ian Smyth, Carolyn Pressman, David J Leffell, Bernard Gerrard, Alisa M Goldstein, Michael Dean, Rune Toftgard, Georgia Chenevix-Trench, Brandon Wainwright, Allen E Bale.
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