The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding pro...

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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 24; no. 18; p. 14196
Main Authors:	Cornelison, Robert, Marrah, Laine, Fierti, Adelaide, Piczak, Claire, Glowczyk, Martyna, Tajammal, Anam, Lynch, Sarah, Li, Hui
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 01-09-2023 MDPI
Subjects:	Actin actin-binding protein advillin Aggression Antimitotic agents Antineoplastic agents AVIL Binding proteins Cancer therapies Cell adhesion & migration Cell cycle Cell division Cell Transformation, Neoplastic Chemotherapy Child Children Clinical trials Colorectal cancer Cytoskeleton Cytotoxicity Drug dosages Families & family life Genes Growth factors Health aspects Humans Metastasis Microfilament Proteins - genetics Muscle proteins Mutation pediatric cancer Pediatrics Pheniramine Protein binding Proteins Radiation therapy Remission (Medicine) Response rates Rhabdomyosarcoma Rhabdomyosarcoma - genetics Stem cells Toxicity advillin rhabdomyosarcoma AVIL actin-binding protein pediatric cancer
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Summary:	Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding proteins, although promising, has historically been challenging. Recent advances have made this possibility more salient, including our lab's identification of advillin (AVIL), a novel oncogenic actin-binding protein that plays a role in many cytoskeletal functions. AVIL is overexpressed in many RMS cell lines, patient-derived xenograft models, and a cohort of 30 clinical samples of both the alveolar (ARMS) and embryonal (ERMS) subtypes. Overexpression of AVIL in mesenchymal stem cells induces neoplastic transformation both in vitro and in vivo, and reversing overexpression through genetic modulation reverses the transformation. This suggests a critical role of AVIL in RMS tumorigenesis and maintenance. As an actin-binding protein, AVIL would not traditionally be considered a druggable target. This perspective will address the feasibility of targeting differentially expressed actin-binding proteins such as AVIL therapeutically, and how critical cell infrastructure can be damaged in a cancer-specific manner.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms241814196