Human Gastrin- Releasing Peptide Receptor Expression in Women with Uterine Cervix Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Feb 10

PMID 36761980

Authors

Charles A Kunos

Denise Fabian

Dana Napier

Mark S Stonecypher

Ravyn M Duncan

Jason Hurt

Affiliations

Soon will be listed here.

Abstract

Introduction: Pb-DOTAM-GRPR1 is a pharmaceutical radioimmunoconjugate consisiting of an α-particle-emitting radionuclide lead-212 (Pb), 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 Pb-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 Pb-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 Pb-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 Pb-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).

Citing Articles

Cisplatin-Containing Combinations Associate with Survival in Women from Appalachian Kentucky with Metastatic, Persistent, or Recurrent Uterine Cervix Cancer.

Kunos C, Miller R, Fabian D Cancers (Basel). 2024; 16(19).

PMID: 39409939 PMC: 11475045. DOI: 10.3390/cancers16193319.

Preclinical Investigation of [Pb]Pb-DOTAM-GRPR1 for Peptide Receptor Radionuclide Therapy in a Prostate Tumor Model.

Saidi A, Stallons T, Wong A, Torgue J J Nucl Med. 2024; 65(11):1769-1775.

PMID: 39327021 PMC: 11533912. DOI: 10.2967/jnumed.124.268101.

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