Introduction Cancer is an unyielding and devastating disease that causes millions of deaths each year. Despite advances in diagnosis and treatment, cancer is still a daunting and mysterious force of nature. Rhabdomyosarcoma, or RMS, is a rare but particularly devastating type of cancer that affects primarily children. This cancer is known for its aggressiveness, posing a great challenge for cancer biologists who are yet to understand the mechanisms and cellular hierarchy leading to the developmental arrest that occurs in RMS. This article aims to discuss what is currently known about the molecular mechanisms, cellular hierarchy, and treatment of RMS, in order to provide a better understanding of this cancer. Overview of Rhabdomyosarcoma Rhabdomyosarcoma is a rare type of cancer that affects mainly children. It is typically classified by histological subtypes, including embryonal, alveolar, and botryoid. It is characterized by malignant rhabdomyoblasts, cells that typically differentiate into skeletal muscle, but in RMS become arrested in developmental stages. While it can occur anywhere in the body, this cancer is most common in the head and neck, including the orbit, genitourinary tract, extremities, and trunk. It is most common in patients younger than age 10, and is the most common soft tissue malignancy in children. Molecular Mechanisms of Rhabdomyosarcoma In order to gain a better understanding of the mechanisms leading to the developmental arrest in RMS, researchers have begun to explore the underlying molecular mechanisms of this cancer. Several genes have been identified as drivers of RMS pathogenesis. TP53 is the most frequent gene alteration found in RMS, with rates of alteration ranging from 33–63%, depending on the subtype. This gene is the most commonly mutated driver in cancer, and it is known to be a major tumor suppressor. Other studies have discovered that loss of PTEN, a tumor suppressor gene, is associated with worse overall survival outcomes in RMS. Additionally, up to 10% of RMS cases have been discovered to have a TP63-driven gene signature, suggesting this gene may have an important role in RMS. Cellular Hierarchy of Rhabdomyosarcoma In order to further understand the development of RMS, researchers have sought to gain an understanding of the cellular hierarchy of this cancer. Studies have found that RMS is associated with the accumulation of certain “cancer stem cells”, or “tumor-initiating cells”, which have an inherent ability to differentiate into multiple types of cells. Specifically, these cells have been observed to have the capacity to differentiate into various types of muscle cells, suggesting they may play a role in the development of RMS. Additionally, research has found that these tumor-initiating cells can lead to the formation of tumors, and are resistant to traditional treatments like chemotherapy and radiation, suggesting they may be responsible for treatment resistance observed in RMS. Treatments for Rhabdomyosarcoma As RMS is a relatively rare cancer, there is still much to be learned about its treatment. Currently, the mainstay of treatment is typically a combination of surgery, radiation, and chemotherapy. Surgery is commonly used to remove tumors, while radiation helps to reduce the size of tumors that cannot be removed surgically. Chemotherapy is used to treat systemic spread of the cancer, and is often utilized in combination with surgery and radiation. Additionally, more targeted treatments are being developed and tested, such as CDK4/6 inhibitors and mTOR inhibitors, in order to more effectively target the molecular pathways involved in RMS. Conclusion Rhabdomyosarcoma is a rare but devastating cancer that disproportionately affects children. While much progress has been made in the diagnosis and treatment of this cancer, much still remains to be learned about the molecular mechanisms and cellular hierarchy of RMS. Research has identified several driver genes and tumor-initiating cells that appear to play a role in the development of RMS. Current treatments are typically a combination of surgery, radiation, and chemotherapy, as well as more targeted treatments such as CDK4/6 inhibitors and mTOR inhibitors. It is hoped that further research will yield new insights into the development and treatment of RMS, so that this cancer may be better understood and effectively treated in the future.
https://www.lifetechnology.com/blogs/life-technology-medical-news/identifying-drug-target-candidates-to-treat-pediatric-rhabdomyosarcoma-tumors
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