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Utilizing feline oral squamous cell carcinoma patients to develop NQO1-targeted therapy
- Source :
- Neoplasia (New York, N.Y.), Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 8, Pp 811-822 (2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Developing effective therapies for the treatment of advanced head-and-neck squamous cell carcinoma (HNSCC) remains a major challenge, and there is a limited landscape of effective targeted therapies on the horizon. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a 2-electron reductase that is overexpressed in HNSCC and presents as a promising target for the treatment of HNSCC. Current NQO1-targeted drugs are hindered by their poor oxidative tolerability in human patients, underscoring a need for better preclinical screening for oxidative toxicities for NQO1-bioactivated small molecules. Herein, we describe our work to include felines and feline oral squamous cell carcinoma (FOSCC) patients in the preclinical assessment process to prioritize lead compounds with increased tolerability and efficacy prior to full human translation. Specifically, our data demonstrate that IB-DNQ, an NQO1-targeted small molecule, is well-tolerated in FOSCC patients and shows promising initial efficacy against FOSCC tumors in proof-of-concept single agent and radiotherapy combination cohorts. Furthermore, FOSCC tumors are amenable to evaluating a variety of target-inducible couplet hypotheses, evidenced herein with modulation of NQO1 levels with palliative radiotherapy. The use of felines and their naturally-occurring tumors provide an intriguing, often underutilized tool for preclinical drug development for NQO1-targeted approaches and has broader applications for the evaluation of other anticancer strategies.
- Subjects :
- Oncology
Cancer Research
medicine.medical_specialty
medicine.medical_treatment
Drug Evaluation, Preclinical
Antineoplastic Agents
Polymorphism, Single Nucleotide
Targeted therapy
Feline
Mice
Palliative radiotherapy
Internal medicine
NAD(P)H Dehydrogenase (Quinone)
medicine
Animals
Humans
Single agent
Basal cell
Molecular Targeted Therapy
RC254-282
Original Research
Comparative oncology
business.industry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Disease Management
Combined Modality Therapy
Immunohistochemistry
Preclinical
Pre-clinical development
Radiation therapy
Feline Oral Squamous Cell Carcinoma
Disease Models, Animal
Treatment Outcome
Tolerability
Mutation
Carcinoma, Squamous Cell
Cats
NQO1
Mouth Neoplasms
Tomography, X-Ray Computed
business
Subjects
Details
- ISSN :
- 14765586
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Neoplasia
- Accession number :
- edsair.doi.dedup.....5346cbd2eae9d7e1a815b7aa63b2c5a6