# Molecular pathways associated with BCC to SCC pathway switching

> **NIH NIH F32** · STANFORD UNIVERSITY · 2020 · $64,926

## Abstract

PROJECT SUMMARY/ABSTRACT:
Basal cell carcinoma (BCC) represents the most common type of skin cancer with more than four million cases
in the US each year. BCCs have the ability to circumvent therapeutics due to their intrinsic tumor plasticity,
allowing for incredible tumor evolution. The identification of non-canonical pathways that drive tumor resistance
has dramatically impacted the understanding of BCC resistance mechanisms, however, the complex tumor
heterogeneity generates a significant knowledge gap, which continues to hamper clinical outcomes. The
observation that BCCs can undergo tumor evolution events (referred to as pathway switching) to squamous
cell carcinoma (SCC) represents a resistance mechanism involving complete alterations in gene expression
programs leading to cancer-type switching. The long-term goal of this proposal is to elucidate the molecular
and transcriptional mechanisms underlying pathway switching with particular emphasis on understanding the
epigenetic regulation at single cell resolution. Preliminary data indicate that SCC-signatures develop early in
tumor progression, which is in part due to differential transcriptional regulation of AP-1 family members, but
what specific transcription factor is not clear. Therefore, the central hypothesis underlying this proposal is that
dynamic epigenetic regulation promotes the acquisition of SCC-like features in BCCs, potentially early on in
tumor development. Aim 1 will uncover the key AP-1 family transcription factor(s) that drive BCC to SCC
pathway switching utilizing a novel in vitro system which can faithfully model this process. Aim 2 takes
advantage of scRNA-Seq datasets from naïve tumors and proposes additional scRNA-Seq along with
scATAC-Seq experiments to define a multi-omic temporal progression of BCC to SCC pathway switching. With
a pipeline to acquire fresh human BCC tumors established and the ability to leverage expertise in single-cell
genomic analysis, the proposed research is highly feasible in the allotted time. The overall rationale for the
proposal is to adequately address a clinically unmet need to understand a key resistant mechanism in BCC.
This highly innovative proposal uses novel tools, coupling an in vitro system to model pathway switching with
single cell gene expression and chromatin analysis of patient samples. This work has great promise to fill a
significant knowledge gap concerning mechanisms of BCC tumor evolution with goals to clear the path for
more targeted and rationale drug therapies.

## Key facts

- **NIH application ID:** 10067239
- **Project number:** 1F32CA254434-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Daniel William Haensel
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067239

## Citation

> US National Institutes of Health, RePORTER application 10067239, Molecular pathways associated with BCC to SCC pathway switching (1F32CA254434-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10067239. Licensed CC0.

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