Leading expert in pediatric oncology and precision medicine, Dr. Shai Izraeli, MD, explains how comprehensive genomic sequencing of every tumor is a critical step in modern cancer care, using a powerful clinical case of an infant with a chemotherapy-resistant tumor who achieved a complete response to a targeted therapy after a TRK fusion was identified.
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Genomic Tumor Sequencing in Pediatric Cancer: A Precision Medicine Case Study
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- The Shift to Precision Medicine in Cancer Treatment
- A Clinical Case: An Infant with a Resistant Tumor
- How Genomic Sequencing Revealed the Target
- Dramatic Response to Targeted Inhibitor Therapy
- The TRK Fusion and Its Implications Across Cancer Types
- The Imperative to Test Genomic Profiles in All Cancers
- A New Era of Cancer Classification and Treatment
The Shift to Precision Medicine in Cancer Treatment
Cancer treatment has fundamentally shifted from a one-size-fits-all approach based on a tumor's tissue of origin to a precision medicine model. This modern paradigm selects targeted therapies based on the unique genetic and molecular profiles of an individual's cancer. Dr. Shai Izraeli, MD, a leading pediatric hematologist-oncologist, emphasizes that Next Generation Sequencing (NGS) and Whole Exome Sequencing (WES) are redefining how we classify and treat cancer.
A Clinical Case: An Infant with a Resistant Tumor
Dr. Shai Izraeli, MD, shares a compelling clinical case that underscores the life-saving potential of genomic testing. A four-month-old infant presented with a massive, aggressive chest wall tumor. The child's cancer progressed despite receiving standard chemotherapy regimens. The prognosis was dire, and the medical team feared the child would not survive.
How Genomic Sequencing Revealed the Target
As a last resort, the team performed comprehensive genomic sequencing on the infant's tumor. This analysis revealed a specific genetic abnormality known as a TRK fusion. Dr. Izraeli, drawing on his expertise in leukemia, recognized this mutation from extremely rare cases of blood cancer. He knew that preclinical research had shown a novel inhibitor medication could effectively target this abnormality in mouse models.
Dramatic Response to Targeted Inhibitor Therapy
Dr. Shai Izraeli, MD, immediately researched the new inhibitor and found an ongoing clinical trial. The infant was enrolled and began treatment. The response was nothing short of miraculous. Photographic evidence showed the massive tumor had visibly shrunk within just two weeks of starting the targeted therapy. After two months, the gross tumor had disappeared completely, achieving a complete response that chemotherapy could not.
The TRK Fusion and Its Implications Across Cancer Types
This case illustrates a core principle of precision medicine: treatment targets the genetic driver of the cancer, not the organ where it originated. The TRK fusion is a potent oncogenic driver found in a small percentage of many cancer types. Dr. Shai Izraeli, MD, notes that while it is present in only about 1% of leukemias, it is found in a significant 30% of brain tumors in children under three years old. This genetic abnormality can occur in brain cancer, blood cancer, and various soft tissue sarcomas, like the infant's chest wall tumor.
The Imperative to Test Genomic Profiles in All Cancers
The critical lesson from this case is that every cancer patient should have their tumor genomically profiled. Sequencing the tumor's DNA can uncover these "actionable" mutations, opening the door to highly effective, targeted treatments. Conversely, patients without a specific genetic abnormality will not benefit from therapies designed to target it, sparing them from unnecessary side effects and ineffective treatment. Dr. Shai Izraeli, MD, states unequivocally that you must test genomics in all cancer cases.
A New Era of Cancer Classification and Treatment
Dr. Anton Titov, MD, and Dr. Izraeli discuss how this approach signifies a new era in oncology. We are moving away from classifying cancer solely by the organ or tissue type and toward a molecular and genetic-based classification system. Cancers from different organs that share the same genetic cause can now be treated as the same disease with a single, effective targeted therapy. This is the true meaning of precision medicine, a transformative shift that is improving outcomes for patients across many areas of oncology.
Full Transcript
Dr. Anton Titov, MD: Treatment of cancer has shifted from treating tumors by tissue origin to selecting targeted therapies. Cancer treatment is based on genetic and molecular profiles of cancer. Next Generation Sequencing (NGS) and Whole Exome Sequencing (WES) redefine classification and methods of cancer treatment.
A leading precision medicine expert and pediatric hematologist-oncologist shares a vivid clinical case.
Dr. Shai Izraeli, MD: A couple of months ago in the department, we had a child with cancer. I show you photos of the child with permission of the parents.
Dr. Anton Titov, MD: The child was four months old. Terrible! You want me to put it on the screen?
Dr. Shai Izraeli, MD: This child had this tumor. His cancer progressed on chemotherapy. We thought he would die. Then we did genomic sequencing of his tumor. We found this genetic abnormality.
Because I'm a leukemia expert, I knew about a very rare case of leukemia with this same genetic mutation abnormality. At that time, this genetic mutation was put into mice. The mice were cured by a new inhibitor cancer medication.
I googled the medication. I found that there was a clinical trial with this new cancer inhibitor. We gave the child this inhibitor in a clinical trial.
This is a picture of the tumor before cancer treatment. This picture is two weeks after starting targeted tumor therapy. Now this is two months later. The gross tumor disappeared completely! Unbelievable!
Dr. Anton Titov, MD: Yes! Now, what is the relevance of this child cancer case example to leukemia?
Dr. Shai Izraeli, MD: Because this is a typical new cancer treatment method at the age of precision medicine. The cancer treatment is against the genetic abnormality. Treatment of the tumor is not against the disease as it is defined by the affected organ.
This genetic abnormality is called TRK. This is an excerpt from a paper that I wrote. It is published in Blood, a journal of hematology oncology.
This genetic mutation is found in many subtypes of cancer. It exists in brain cancer, blood cancer. This child’s cancer was a chest wall cancer, but it is a very rare cancer.
What is the implication? The implication is that you have to test genomics. You must sequence DNA in all cancer cases. Because if you find this genetic abnormality, then you can treat it with the new inhibitor. It is a targeted chemotherapy.
But there is no benefit to using other cancer medications for patients that don't have this genetic abnormality in their cancer.
Dr. Anton Titov, MD: In other words, when we deal with precision medicine, we don't anymore deal with only a specific disease.
Dr. Shai Izraeli, MD: We do not deal with only leukemia or brain cancer. This type of cancer is a soft tissue cancer. But cancers from different organs are caused by the same cause. Then tumors may be treated as the same disease.
I have several such examples. This is not the only one example of child cancer. This is really the age of precision medicine. That's the meaning of precision medicine.
It happens in many areas of oncology. You move from classification of cancer by the organ or by the tissue. You move to the classification of cancerous tumors based on genetic and molecular signature.
We can use this example. This is a solid tumor; it's not a leukemia. But it's very relevant to leukemias. Because only 1% of leukemias have this molecular abnormality, TRK mutation. But 30% of brain tumors below the age of three have this molecular abnormality, TRK.