Rhabdomyosarcoma Advanced Treatments in 2022

1. Introduction

Rhabdomyosarcoma (RMS) is a relatively rare cancer that arises from immature cells with the ability to differentiate into skeletal muscle cells later. RMS can arise from soft tissues, such as the skeletal muscle, connective tissue, bone, bladder, prostate, testis, nose, orbit, and anus [1]. Researchers show that approximately 70% of the RMS patients can be diagnosed before age of 10 years on top of that RMS can develop in adolescents and adults. There are different types of RMS as follows.



  • Embryonal Rhabdomyosarcoma (ERMS)

  • Alveolar Rhabdomyosarcoma ( (ARMS)

  • Pleomorphic Rhabdomyosarcoma (PRMS)

  • Spindle cell/sclerosing Rhabdomyosarcoma (SRMS)

  • Botryoid Rhabdomyosarcoma

The international classification of Rhabdomyosarcoma includes botryoid and spindle cell RMS as superior-risk groups, Embryonal RMS as an intermediate-risk group, and alveolar RMS as an unfavorable-risk group[2]. Chromosomal translocations of t(2;13)(q35;q14) or t(1;13)(q36;q14) are detected in most patients with ARMS. Approximately 60% of the patients with ARMS express PAX3-FOXO1 and 20% of those express PAX7-FOXO1 [3,4]. PAX-FOXO1 chimeric protein functions as an active transcription factor, leading to oncogenic transformation by inducing the expression of abnormal genes. Reports show specific chimeric genes are not associated with ERMS and the other types of RMS; however, these tumors are often associated with various chromosomal abnormalities, which, in turn, lead to the inactivation of the tumor suppressor gene p53 pathway [5,6]. A major type of treatment for RMS is as follows.


  • Chemotherapy (vincristine, actinomycin D, and cyclophosphamide/ifosfamide)

  • Molecular Targeted Drugs

  • Radiation Therapy

  • Immunotherapy

  • Novel Therapeutic Approaches

  • Surgery

  • Palliative Care


This article reviews an overview of RMS and its advanced Treatment of it. All the treatments will be depending on the following factors.


  • Stage of the disease

  • Type of RMS

  • Overall health and preferences of the patient

  • The possible side effects



2. Chemotherapy for Rhabdomyosarcoma

Multi-drug chemotherapy regimens significantly improved the outcome in patients with localized RMS, although no marked improvement has been observed in patients with metastatic RMS [7]. Standard chemotherapy regimens for RMS in North America include vincristine, actinomycin D, and cyclophosphamide (VAC), whereas those in Europe include ifosfamide, vincristine, and actinomycin D (IVA) [8,9,10]. A clinical trial was conducted to assess the efficacy of a modified chemotherapy regimen for reducing treatment-associated toxicity in RMS patients. The report shows that VAC/VI regimen is a candidate for alternative standard therapy in patients with intermediate-risk RMS[11].

There was an issue that high-dose chemotherapy improve the outcomes compared to standard chemotherapy in patients with metastatic RMS. However, it was reported that a significant improvement was not observed in patients treated with high-dose chemotherapy compared to that in those treated with standard chemotherapy, although an increased incidence of treatment-related adverse events (AEs) was observed in patients with high-dose chemotherapy [12].


3. Molecular Targeted Drugs for Rhabdomyosarcoma

Molecularly targeted drugs were introduced to reduce the harm of conventional drugs to the normal cells of the patient. Molecularly targeted drugs are thought to specifically attack cells with target molecules involved in the growth and proliferation of cancer cells[13]. Vascular endothelial growth factor receptor(VEGFR) regulates physiologic angiogenesis, and tumor cells induce pathologic angiogenesis via the production of VEGF [14]. Therefore, VEGF is considered a therapeutic target in cancer. RMS is only a small population of these studies therefore it is difficult to assess the efficacies of the agents in patients with RMS. Recent reports show the importance of the Mechanistic target of rapamycin (mTOR) inhibitors for RMS targeted therapy. It stops the protein that helps cells divide and survive. According to cancer researchers, many studies focused on the Sirolimus, as a type of mTOR inhibitor treatment for recurrent rhabdomyosarcoma. Many studies highlighted tyrosine kinase inhibitors. Such as MK-1775, cabozantinib-s-malate, and palbociclib are tyrosine kinase inhibitors being studied in the treatment of recurrent rhabdomyosarcoma. Not only that but also Tyrosine kinase inhibitors block signals that cancer cells need to grow and divide[15].




4. Radiation Therapy for Rhabdomyosarcoma

Radiation Therapy (RT) has been identified as one of the standard treatments for RMS patients. RT uses beams of intense energy to fight against cancer cells. Patients with RMS are stratified into the low, intermediate, and high-risk groups according to the tumor location, size, histological subtype, Involvement of lymph node, metastatic lesion, and surgical margin [16]. RT induces various complications and long-term safety of the treatment is essential in pediatric patients with destructive.


5. Immunotherapy for Rhabdomyosarcoma

Several basic and clinical studies of RMS show that the immune checkpoint axis is a strong therapeutic target in various malignancies Recently, adoptive T-cell therapy (ACT) has been considered a promising treatment for cancer [16,17,18,19,20]. A protein found on T cells helps keep the body's immune responses in check. CTLA-4 is a protein on the surface of T cells that attaches to another protein called B7 on a cancer cell, it stops the T cell from killing the cancer cell. Cancer studies show CTLA-4 inhibitors attach to CTLA-4 and allow the T cells to kill cancer cells. In the treatment of childhood rhabdomyosarcoma, Ipilimumab is being studied.


PD-1 and PD-L1 Inhibitor Therapy: The summary of this therapy as follows. PD-1 is a protein on the surface of T cells that helps keep the body’s immune responses in check. PD-L1 is a protein found on some types of cancer cells. When PD-1 attaches to PD-L1, it stops the T cell from killing the cancer cell. PD-1 and PD-L1 inhibitors keep PD-1 and PD-L1 proteins from attaching to each other. So it allows the T cells to kill cancer cells. Therefore Nivolumab and pembrolizumab are types of PD-1 inhibitors that are being studied in the treatment of childhood rhabdomyosarcoma that has come back or progressed during treatment[14].


6. Therapeutic Approaches for Rhabdomyosarcoma

Multidisciplinary approaches to the management of RMS are highly considered in recent clinical studies. Recent basic studies have shown promising therapeutic approaches, including ferroptosis agents, oncolytic virus, and tumor-targeting bacterial therapy [13]. Ferroptotic agents may be promising treatments for RMS.


7. Surgery for Rhabdomyosarcoma

In some cases of RMS Surgery is the single most critical therapy, especially for pediatric rhabdomyosarcoma of the head and neck (HNRMS). However, very few studies have explored the surgical management of pediatric rhabdomyosarcoma of the head and neck (HNRMS) and there is no standard surgical protocol[21]


8. Palliative care for Rhabdomyosarcoma

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. Patients may also receive palliative treatments similar to those meant to get rid of cancer, such as chemotherapy, surgery, or radiation therapy [22].


Takeaway messages


There are many advanced treatment regiments from targeted therapy to immunotherapy that are being actively researched and practiced in the United States. Using our global telehealth platform, you can now receive a virtual consultation with a top physician specialist in America, no matter where you live in the world. Regardless of your condition and your country, we are here to help you. Contact us in the below form to learn how we can provide world-class care to you and your loved ones.


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