The Capacity of Drug-Metabolising Enzymes in Modulating the Therapeutic Efficacy of Drugs to Treat Rhabdomyosarcoma.
Enric Arasanz PicherWahajuddin MuhammadStefan BarthJulia C ChisholmJanet ShipleyKlaus PorsPublished in: Cancers (2024)
Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma (STS) that predominantly affects children and teenagers. It is the most common STS in children (40%) and accounts for 5-8% of total childhood malignancies. Apart from surgery and radiotherapy in eligible patients, standard chemotherapy is the only therapeutic option clinically available for RMS patients. While survival rates for this childhood cancer have considerably improved over the last few decades for low-risk and intermediate-risk cases, the mortality rate remains exceptionally high in high-risk RMS patients with recurrent and/or metastatic disease. The intensification of chemotherapeutic protocols in advanced-stage RMS has historically induced aggravated toxicity with only very modest therapeutic gain. In this review, we critically analyse what has been achieved so far in RMS therapy and provide insight into how a diverse group of drug-metabolising enzymes (DMEs) possess the capacity to modify the clinical efficacy of chemotherapy. We provide suggestions for new therapeutic strategies that exploit the presence of DMEs for prodrug activation, targeted chemotherapy that does not rely on DMEs, and RMS-molecular-subtype-targeted therapies that have the potential to enter clinical evaluation.
Keyphrases
- end stage renal disease
- locally advanced
- ejection fraction
- newly diagnosed
- young adults
- chronic kidney disease
- prognostic factors
- clinical evaluation
- early stage
- stem cells
- peritoneal dialysis
- small cell lung cancer
- emergency department
- risk assessment
- minimally invasive
- cardiovascular disease
- type diabetes
- radiation therapy
- drug delivery
- risk factors
- cancer therapy
- signaling pathway
- drug induced
- radiation induced
- bone marrow
- acute coronary syndrome
- rectal cancer
- mesenchymal stem cells
- patient reported
- diabetic rats
- atrial fibrillation