Human gastrin- releasing peptide receptor expression in women with uterine cervix cancer

Charles A Kunos; Denise Fabian; Dana Napier; Mark S Stonecypher; Ravyn M Duncan; Jason Hurt

doi:10.3389/fonc.2023.1126426

Human gastrin- releasing peptide receptor expression in women with uterine cervix cancer

Front Oncol. 2023 Jan 25:13:1126426. doi: 10.3389/fonc.2023.1126426. eCollection 2023.

Authors

Charles A Kunos¹, Denise Fabian¹, Dana Napier², Mark S Stonecypher³, Ravyn M Duncan³, Jason Hurt⁴

Affiliations

¹ Department of Radiation Medicine, University of Kentucky, Lexington, KY, United States.
² Biospecimen Procurement & Translational Pathology, University of Kentucky, Lexington, KY, United States.
³ Molecular Pathology Laboratory Network, Inc., Maryville, TN, United States.
⁴ Orano Med LLC, Plano, TX, United States.

Abstract

Introduction: ²¹²Pb-DOTAM-GRPR1 is a pharmaceutical radioimmunoconjugate consisiting of an α-particle-emitting radionuclide lead-212 (²¹²Pb), a metal chelator DOTAM (1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane), and a gastrin-releasing peptide receptor (GRPR)-targeted antagonist currently being evaluated as therapy in uterine cervix and other cancer types. Previous studies have revealed that a variable proportion of uterine cervix cancer tumors overexpress the radiopharmaceutical target GRPR when assessed by cell proportion and staining intensity immunoreactive scores (IRS). Tumor response to ²¹²Pb-DOTAM-GRPR1 strongly associates with GRPR overexpression, and therefore, it seems reasonable to assess uterine cervix cancer GRPR immunoreactivity for greater insight into the feasibility of using ²¹²Pb-DOTAM-GRPR1 as a radiopharmaceutical treatment.

Methods: We examined a series of 33 uterine cervix cancer paraffin-embedded tumors in order to establish whether this tumor type overexpresses GRPR at an IRS score of 6 or higher, as ²¹²Pb-DOTAM-GRPR1 is currently being evaluated in clinical trials against tumors showing such a level of expression.

Results: The results show that five of five (100%) primary adenocarcinomas and 10 of 16 (63%) primary squamous cell tumors overexpress GRPR at an IRS score of 6 or higher.

Discussion: The frequency of overexpression in this study suggests that ²¹²Pb-DOTAM-GRPR1 radiopharmaceutical treatment may be useful in the management of persistent, recurrent, or metastatic uterine cervix cancer patients. A phase I clinical trial involving patients with metastatic uterine cervix cancer is currently underway (NCT05283330).

Keywords: cervical cancer; gastrin-releasing peptide (GRP) receptor; radiopharmaceutical; uterine cervix adenocarcinoma; uterine cervix cancer.

Associated data

ClinicalTrials.gov/NCT05283330

Grants and funding

This work was supported by NCI grant P30CA177558, which supports the Biospecimen Procurement and Translational Pathology and Biostatistics and Bioinformatics Shared Resource Facilities of the University of Kentucky Markey Cancer Center.