HER Tyrosine Kinase Family and Rhabdomyosarcoma: Role in Onset and Targeted Therapy

Abstract

Rhabdomyosarcomas (RMS) are tumors of the skeletal muscle lineage. Two main features allow for distinction between subtypes: morphology and presence/absence of a translocation between the PAX3 (or PAX7) and FOXO1 genes. The two main subtypes are fusion-positive alveolar RMS (ARMS) and fusion-negative embryonal RMS (ERMS). This review will focus on the role of receptor tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that is comprised EGFR itself, HER2, HER3 and HER4 in RMS onset and the potential therapeutic targeting of receptor tyrosine kinases. EGFR is highly expressed by ERMS tumors and cell lines, in some cases contributing to tumor growth. If not mutated, HER2 is not directly involved in control of RMS cell growth but can be expressed at significant levels. A minority of ERMS carries a HER2 mutation with driving activity on tumor growth. HER3 is frequently overexpressed by RMS and can play a role in the residual myogenic differentiation ability and in resistance to signaling-directed therapy. HER family members could be exploited for therapeutic approaches in two ways: blocking the HER member (playing a driving role for tumor growth with antibodies or inhibitors) and targeting expressed HER members to vehiculate toxins or immune effectors.

Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational Research

“…Many attempts have been made to develop mouse models of other pediatric solid tumors carrying fusion genes, but most of them were unsuccessful or did not achieve the expected tumor occurrence. SyS is one of the few human tumors induced by a unique specific gene translocation that researchers have been able to reproduce in transgenic mice [31][32][33][34][35][36] with high tumor histotype fidelity and obtaining high tumor penetrance.…”

Quantum Dot-Based Screening Identifies F3 Peptide and Reveals Cell Surface Nucleolin as a Therapeutic Target for Rhabdomyosarcoma

“…The following are available online at , Table S1: Peptides used in this study; Table S2: Published work supporting expression of selected targets in RMS cell lines or tumors; Figure S1: Targeted receptors’ expression in RMS cell lines, tumors, and skeletal muscles; Figure S2: Targeted receptors’ expression in RMS cell lines, tumors, and normal tissues; Figure S3: Expression of selected surface targets including nucleolin and p32 in RMS cell lines, tumors, and skeletal muscle; Figure S4: Quality control for conjugation of Streptavidin-QD and biotin-peptides by B4F-quenching; Figure S5: Surface expression of NCAM1 on RMS cell lines and control cells; Figure S6: Surface detection of nucleolin on RMS cells [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ].…”