fig6

Figure 6. Combined therapeutic regimens against RMS. Dual inhibition of the RAS and PI3K pathways has generally proven ineffective due to the emergence of MDR mechanisms and is further limited in clinical settings by toxicity. More promising therapeutic approaches involve monotargeting of either the RAS or PI3K pathway in combination with agents targeting downstream effectors - such as those involved in alternative oncogenic signaling, apoptotic resistance, DDR and drug transport. These combined strategies, aimed at overcoming MDR in RMS, include both ongoing therapies and emerging experimental approaches. RMS: Rhabdomyosarcomas; RAS: rat sarcoma; PI3K: phosphoinositide 3-kinase; MDR: multidrug resistance; DDR: DNA damage response; NF-κB: nuclear factor kappa B; YAP: yes-associated protein; TAZ: transcriptional co-activator with PDZ-binding motif; TEAD: TEA domain family member.