Targeting RHAMM in Cancer - Crosstalk with Non-Coding RNAs and Emerging Therapeutic Strategies Including Peptides, Oligomers, Antibodies, and Vaccines

Sep 23, 2026

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Cancer remains a major cause of mortality worldwide, driven by complex molecular mechanisms that promote metastasis and resistance to therapy. The receptor for hyaluronan-mediated motility (RHAMM) functions as a multifunctional regulator, supporting cell motility, invasion, proliferation, and fibrosis. RHAMM is modulated by noncoding RNAs, including miRNAs, lncRNAs, and circRNAs, and represents a promising therapeutic target. Recent RHAMM-targeted approaches include function-blocking peptides, HA oligomers, anti-RHAMM antibodies, and peptide vaccines such as RHAMM-R3, showing immunogenicity and anti-leukemia efficacy, and suggesting potential to enhance CD8+ T-cell responses and precision cancer treatment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Abstract

1. Introduction

RHAMM and ncRNAs in cancer progression

Therapeutic strategies targeting RHAMM

2. Structural and Molecular Regulation of RHAMM Expression and Function

2.1. Gene Location and Basic Characteristics

Review Targeting RHAMM in Cancer: Crosstalk with Non-Coding RNAsand Emerging Therapeutic Strategies Including Peptides, Oligomers, Antibodies, and Vaccines Dong Oh Moon Academic Editor: ErikA.C. Wiemer Received: 1 July 2025 Revised: 18 July 2025 Accepted: 24 July 2025 Published: 25 July 2025 Citation: Moon, D.O. Targeting RHAMMin Cancer: Crosstalk with Non-Coding RNAsand Emerging Therapeutic Strategies Including Peptides, Oligomers, Antibodies, and Vaccines. Int. J. Mol. Sci. 2025, 26, 7198 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms26157198 Copyright: © 2025 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . Department of Biology Education, Daegu University, 201, Daegudae-ro, Gyeongsan-si 38453, Gyeongsangbuk-do, Republic of Korea; [domoon@daegu.ac.kr; Tel./Fax: +82-53-852-6992](domoon@daegu.ac.kr; Tel./Fax: +82-53-852-6992) Abstract Cancer remains a major cause of mortality worldwide, driven by complex molecular mechanisms that promote metastasis and resistance to therapy. Receptor for hyaluronan-mediated motility (RHAMM) has emerged as a multifunctional regulator in cancer, contributing to cell motility, invasion, proliferation, and fibrosis. In addition to being regulated by noncoding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, RHAMM serves as a promising therapeutic target. Recent developments in RHAMM-targeted strategies include function-blocking peptides (e.g., NPI-110, NPI-106, and P15-1), hyaluronan (HA) oligomers, and anti-RHAMM antibodies, all shown to modulate tumor stroma and suppress tumor invasiveness. Importantly, RHAMM-targeted peptide vaccines, such as the RHAMM-R3 epitope, have demonstrated immunogenicity and anti-leukemia efficacy in both pre-clinical and early clinical studies, suggesting their potential to elicit specific CD8+ T-cell responses and enhance graft-versus-leukemia effects. This review summarizes the intricate roles of RHAMM in cancer progression, its modulation by ncRNAs, and the translational promise of novel RHAMM-targeting approaches, providing insights into future directions for precision cancer therapy. Keywords: RHAMM; non-coding RNAs; peptide inhibitors; HA oligomers; antibodies; peptide vaccines 1. Introduction Cancer, a multifaceted and intricate disease, continues to challenge the scientific community with its complexity and resilience [1,2] . Central to this complexity is the interplay between various molecular actors, among which RHAMM and ncRNAs standout for their critical roles in tumor biology. RHAMM, a co-receptor for hyaluronan, has been implicated in various cellular processes essential for cancer progression, including cell migration, proliferation, and invasion [3,4] . Its relevance in cancer is underscored by its association with poor prognosis and increased metastatic potential in several cancer types. Parallelly, ncRNAs, which include miRNAs, lncRNAs, and circRNAs, have emerged as key regulatory molecules in gene expression [5,6] . Their role in cancer encompasses the modulation of oncogenes and tumor suppressors, influencing every stage of cancer development from initiation to metastasis. The ability of ncRNAs to regulate a wide spectrum of biological functions positions them as central figures in post-transcriptional regulation, affecting cellular behavior in the oncogenic context. The interaction between RHAMM and ncRNAs represents a novel and compelling facet of cancer research, offering potential insights into the mechanisms driving cancer progression. This crosstalk could elucidate previously unknown pathways of cancer development, revealing how these interactions contribute to hallmarks of cancer such as sustaine

FAQs

What roles does RHAMM play in cancer progression?

RHAMM is described as a multifunctional regulator that contributes to cell motility, invasion, proliferation, and fibrosis. It is also linked to poor prognosis and increased metastatic potential in multiple cancer types.

How do non-coding RNAs (ncRNAs) relate to RHAMM?

The review states that RHAMM is regulated by ncRNAs, including miRNAs, lncRNAs, and circRNAs. It emphasizes that the RHAMM–ncRNA interaction offers insights into mechanisms driving cancer progression.

What therapeutic strategies targeting RHAMM are highlighted?

The document summarizes function-blocking peptides, HA oligomers, anti-RHAMM antibodies, and RHAMM-targeted peptide vaccines (e.g., RHAMM-R3). These approaches are reported to modulate tumor stroma, suppress invasiveness, and induce immune responses such as CD8+ T-cell activity.

Sep 23, 2026

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