Study of the Week: Could EGFR Inhibitors Prevent Rhabdomyosarcoma Recurrence?

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.


This week’s study is…

The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma

We previously published about this research in a story titled “Study: Finding Treatments to Prevent Rhabdomyosarcoma Recurrence” which can be found here. This study was first published in the scientific journal Developmental Cell. You can view the abstract of the study here.

This study was affiliated with the St. Jude’s Children’s Research Hospital.

What Happened?

Rhabdomyosarcoma is a form of soft tissue sarcoma that often affects children and young people. It is noted for its ability to recur even after intensive treatment in many cases. Therefore, discovering an approach that could prevent or reduce the ability of rhabdomyosarcoma to recur is important for improving outcomes in this cancer. 

A team of scientists sought to study the group of cancer cells in the tumor that are known to survive after treatment in order to understand how they are able to resist and cause the recurrence of the cancer. Looking at these cells in the lab setting, the researchers used techniques such as single nucleus and single cell RNA sequencing and found these these cells had an interesting trait: they recapitulated, or mirrored, the spectrum of embryonal myogenesis.

This is an early developmental state that, as found in earlier studies, can be responsive to a class of treatments known as epidermal growth factor receptor (EGFR) inhibitors. The approach used matched patient samples as well as orthotopic, patient-derived xenographs that can capture the complexity and biology of human tumors more accurately than other approaches.

In a typical treatment regimen, such as chemotherapy, the most proliferative elements of the tumor are eliminated, but an immature population of cells that have paraxial mesoderm-like features is able to expand and allow for the tumor to begin returning to its original state. However, these cells are dependent on EGFR signaling, meaning that they should be vulnerable to EGFR inhibitor therapy.

In effect, this could give physicians an approach that treats the entirety of the spectrum of cells in a tumor, and could be a strategy with applications in other forms of pediatric cancer as well.

About Rhabdomyosarcoma

Rhabdomyosarcoma is a type of soft tissue sarcoma cancer. It is highly aggressive and affects skeletal muscle cells that are not yet fully differentiated. Most people affected by the disease are under age 18. In many cases, the cause of rhabdomyosarcoma remains a mystery, and the cancer often appears sporadically. However, increased risk has been associated with certain genetic disorders, and parental use of cocaine and marijuana may also increase the risk. The symptoms and presentation of this cancer vary widely and often depend on where the tumor appears; often a prominent lump is noticeable. This means that this cancer can, in some cases, be diagnosed early. Treatment approaches include surgery, chemotherapy, radiation, and immunotherapy. Outcomes vary substantially depending on location, but the cure rate for cancer that hasn’t spread is 75 percent. Relapsed or metastatic cancer has much worse survival rates. To learn more about rhabdomyosarcoma, click here.

Why Does it Matter?

In many types of cancer, treatment outcomes vary greatly depending on whether it can be removed through surgery or can be controlled before it has begun the process of metastasis (spreading from the origin site of the tumor). In rhabdomyosarcoma, outcomes are much worse in cases when surgery isn’t an option or metastasis has occurred. Therefore, finding methods that could help prevent cancer from recurring could help make a difference for a lot of patients.

The results of this study give researchers a new direction to begin testing treatments of the EGFR inhibitor class as a part of therapy in rhabdomyosarcoma:

 “We have a proof of concept that if you target those rare cells that persist with an EGFR inhibitor and combine that with chemotherapy you get a much better outcome because you’re treating the entire . This reflects a different way of thinking about therapy that isn’t focused just on initial response.” – Anand Patel, M.D., Ph.D., St. Jude Department of Oncology, first author

The scientists were able to pinpoint how the cancerous cells went through many of the different stages of muscle cell development, and the cells that were in the earlier stages were the ones that have often been able to avoid destruction when using chemotherapy or other approaches. Now, future studies will be able to test the proof of concept discovered in this research.

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