# Lung cancer prevention and treatment by targeting ALDH1 and CD44 expressing putative lung cancer stem cells

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $352,275

## Abstract

PROJECT SUMMARY
Lung cancer is the leading cause of cancer-related death in the United States. About 90% of lung cancer cases
are associated with genetic/epigenetic changes induced by tobacco smoke (TS). Although all types of lung
cells could be affected by TS, the effect on stem cells is particularly alarming owing to their longevity and
propensity for transformation. Therefore, selective targeting of altered stem cells known as cancer stem cells
(CSCs) could prevent the development of lung cancer. In this application, we will test the hypothesis that
targeting of uniquely tumorigenic putative CSCs expressing high levels of aldehyde dehydrogenase 1(ALDH1H)
and CD44 (CD44H) with the combination of the repurposed drugs disulfiram (DSF) and sulfasalazine (SAS)
which are nano-formulated to enhance bioavailability will suppress the development and progression of
carcinogen-induced and spontaneous lung tumor in mice. These hypotheses will be tested by the following
three specific aims:
Specific Aim 1: Determine the efficacy of SLN-DSF, SLN-SAS and SLN-DSF+SAS to suppress NNK- or
mutant K-ras induced lung tumorigenesis by targeting ALDH1HCD44H subpopulations of lung cells. In this aim,
mice treated with NNK or harboring mutations in K-ras gene will be given the drugs and modulation of tumor
burden, frequency of ALDH1HCD44H lung tumor cells and CSC-associated proteins will be analyzed.
Specific Aim 2: Determine the immunosuppressive effects of ALDH1HCD44H putative LCSCs and whether the
anti-cancer effects of SLN-DSF-SAS are mediated, at least in part, via immunomodulatory mechanism and its
potential to enhance the therapeutic efficacy of anti-PD-L1 immune checkpoint inhibitors. Hypothesis:
Overexpression of PD-L1 by ALDH1HCD44H lung tumor cells endows them immunosuppressive properties and
modulation of these properties by SLN-DSF-SAS could potentiate anti-PD-L1-induced rescuing of
dysfunctional cytotoxic T cells and tumor destruction.
Specific Aim 3: Determine the role of common NSCLC genetic alterations in the generation, proliferation, self-
renewal, and tumor propagating efficiency of ALDH1HCD44H putative CSCs and if these effects are modulated
by SLN-DSF+SAS. Hypothesis: The genotype of transformed lung cells could be an important determinant of
the self-renewal and tumor-propagating potential of ALDH1H CD44H fractions.
Impact: Targeting ALDH1H CD44H putative CSCs is a new paradigm shift in lung cancer prevention and
treatment as these cells are believed to be the cell of origin of cancer.

## Key facts

- **NIH application ID:** 10019474
- **Project number:** 5R01CA231210-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Fekadu Kassie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,275
- **Award type:** 5
- **Project period:** 2019-09-17 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019474

## Citation

> US National Institutes of Health, RePORTER application 10019474, Lung cancer prevention and treatment by targeting ALDH1 and CD44 expressing putative lung cancer stem cells (5R01CA231210-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10019474. Licensed CC0.

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