Precision Medicine in Pediatric Cancer: How Genomic Testing Guides Targeted Therapy

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• Precision Medicine in Pediatric Cancer
• Clinical Case: The Congenital Tumor
• Genomic Testing Reveals a TRK Mutation
• Targeted Therapy with Larotrectinib
• Beyond Tissue of Origin: A New Cancer Classification
• A Second Case: FLT3 Leukemia and Quizartinib
• The Future of Pediatric Oncology

Precision Medicine in Pediatric Cancer

Precision medicine represents a fundamental shift in pediatric cancer treatment. This approach involves selecting targeted cancer therapy based on the unique genetic mutations found within a child's tumor. As Dr. Shai Izraeli, MD, explains, treatment decisions are no longer based solely on a tumor’s tissue or organ of origin. Instead, oncologists use advanced genomic sequencing to identify specific molecular drivers of cancer. This strategy can completely change the course of treatment and lead to a cure, even in the most complex cases.

Clinical Case: The Congenital Tumor

Dr. Shai Izraeli, MD, shares a powerful clinical vignette that illustrates the impact of precision medicine. His team treated an infant who was born with a large congenital tumor attached to his chest. The massive tumor, described as being the size of a small football, was diagnosed when the baby was four months old. The cancer was deemed inoperable due to its size and location. Initial treatment with standard chemotherapy regimens failed completely. Dr. Shai Izraeli, MD, notes that despite chemotherapy, the aggressive tumor continued to grow, creating a dire and seemingly hopeless situation for the child and his family.

Genomic Testing Reveals a TRK Mutation

Faced with a treatment-resistant cancer, the medical team decided to perform comprehensive genomic testing on the tumor. This decision was critical. The genomic sequencing revealed a specific genetic abnormality in a gene called NTRK (often referred to as "TRK"). Dr. Shai Izraeli, MD, recognized this mutation immediately. He had recently read a clinical report about an extremely rare case of leukemia that harbored the exact same TRK genetic abnormality. In that reported case, researchers had transplanted the human leukemia into mice and successfully cured them using an experimental TRK inhibitor. Dr. Izraeli then researched online and discovered that this TRK inhibitor, later identified as larotrectinib, was already in clinical trials for human patients.

Targeted Therapy with Larotrectinib

The discovery of the TRK mutation opened a new therapeutic pathway. The child was enrolled in a clinical trial in Germany to receive the targeted TRK inhibitor, larotrectinib. The results were nothing short of miraculous. The medication, administered as an oral syrup, began working within two weeks. Dr. Shai Izraeli, MD, reports that 90% of the massive tumor had disappeared in that short timeframe. Within a couple of months, the tumor had almost completely vanished. The small residual amount of cancer that remained was then small enough to be safely removed with surgery. This case demonstrates how a genetically-targeted "magic bullet" can achieve what months of conventional chemotherapy could not.

Beyond Tissue of Origin: A New Cancer Classification

This clinical case underscores a major paradigm shift in oncology. Dr. Shai Izraeli, MD, emphasizes that tumors are no longer classified solely by their tissue of origin, such as leukemia, sarcoma, or carcinoma. Today, classification is increasingly based on the specific genetic abnormalities that drive the cancer's growth. TRK mutations, for example, are rare but can be found across many different cancer types, including brain gliomas, kidney cancers, and soft tissue tumors. Because these mutations are actionable—meaning there is a targeted drug designed to inhibit them—finding them through genomic testing is essential for every child with cancer. This approach ensures that a patient receives the most precise and effective treatment available.

A Second Case: FLT3 Leukemia and Quizartinib

Dr. Izraeli provides another compelling example of precision medicine's success, this time in acute myeloid leukemia (AML). He treated a child whose leukemia did not respond to any standard chemotherapy. Genomic profiling of the leukemia cells revealed an activation of a signaling molecule called FLT3. This specific genetic alteration made the cancer aggressive and treatment-resistant. The child was then treated with a high-dose FLT3 inhibitor, such as quizartinib. This targeted approach pushed the leukemia into remission, and the child is now cured. This case further proves that identifying and targeting the root genetic cause of cancer can lead to successful outcomes where conventional treatments fail.

The Future of Pediatric Oncology

The era of precision medicine is an incredibly exciting time in pediatric oncology. Dr. Shai Izraeli, MD, believes that the approach of testing every child's cancer for a wide array of genetic abnormalities will become standard practice. While he cautions that these targeted therapies are not without side effects and are not a universal solution, they represent a monumental leap forward. The accumulation of these "magic bullets" means that more children with rare and difficult-to-treat cancers will have effective options. Dr. Izraeli concludes with a powerful sense of optimism, stating his belief that the era where every child with cancer can be cured is within reach for the next generation of doctors.

Full Transcript

Dr. Anton Titov, MD: Precision medicine means we have to select targeted cancer treatment based on unique tumor mutations. Treatment is not based only on a tumor’s tissue or organ origin.

A top pediatric cancer expert shares a remarkable patient’s story. It illustrates how tumor genomic sequencing can change the course of cancer treatment and result in a cure.

Professor Izraeli, is there a clinical case about a pediatric cancer patient that you could discuss? A situation that illustrates some of the topics we discussed about pediatric cancers, and in particular, childhood leukemias?

Dr. Shai Izraeli, MD: Maybe I'll give you an example that is not from a leukemia case. But I'm very moved by this child cancer treatment example. We were very excited by this clinical case.

It just tells you the general importance of precision medicine across different types of tumors. We do precision medicine pediatric cancer therapy here in our hospital. We are not a leukemia department only. We treat all types of cancers.

We had a child with a congenital tumor. He was born with a tumor, but he was diagnosed only four months later. Then he had a tumor almost like a small football attached to his chest.

The type of tumor is not so important, but his cancer was not operable. We treated this tumor with chemotherapy, but it grew and grew despite chemotherapy.

Then we decided to do genomic testing of the tumor. In the cancer genome, we found a genetic abnormality in a gene called TRK, "Trek".

I was very excited when I saw this genetic abnormality in this child’s cancer. I was very excited because a couple of months before, I saw a clinical report from another hospital on an extremely rare case of leukemia. It had exactly the same TRK genetic abnormality.

At that time, there was no cancer medication available for this abnormality. But oncologists transplanted the leukemia into mice. Then they treated the mice with a TRK inhibitor. The mice were cured from leukemia.

Then, as you know, I'm an important doctor, right? What are important doctors doing? They go to Doctor Google, right?

I went to Doctor Google. This TRK cancer inhibitor was already in clinical trials.

Now we returned to this child. He had a very big tumor attached to his ribs. We treated him with this new TRK inhibitor [larotrectinib] in a clinical trial in Heidelberg, Germany. Now this clinical trial is opened here.

The tumor disappeared completely! TRK inhibitor cancer medication is given as a syrup, by mouth, orally. Already within two weeks, 90% of the cancer tumor was gone.

Now, a couple of months later, the tumor almost disappeared. The rest of the cancer we can remove by surgical operation.

Now, why do I decide to give you an example of a solid tumor? You asked me to give a clinical vignette of leukemia?

Dr. Anton Titov, MD: You already understand it.

Dr. Shai Izraeli, MD: Because I knew about this TRK inhibitor from leukemia. But this already is the hallmark of precision medicine cancer therapy today.

Because these TRK genetic mutations in the tumor are rare. These abnormalities are not common, but they are not unique to the type of tumor that I described. They are not unique to leukemia, where they are extremely rare.

These tumor mutations are also found in brain gliomas. TRK mutations exist in kidney cancer and other cancers. These cancer genetic abnormalities happen in a small percentage of tumors.

But this example tells you why it's really important today to test every child with cancer for general genetic abnormalities. Because we may find a genetic abnormality that can be treated by a specific targeted cancer medication.

Then we should use a targeted cancer medication and not something else. That is what we are going to do in the upcoming year. That's an example of modern precision medicine.

Dr. Anton Titov, MD: Classification of tumors is not done only by the type of tissue that the tumor comes from. Examples are leukemia, soft tissue tumors, carcinomas, brain tumors.

Today tumors are classified based on a genetic abnormality that causes cancer. That's one example.

Another example of targeted cancer therapy is this. We had a child with acute myeloid leukemia. Leukemia didn't respond to any treatment.

Dr. Shai Izraeli, MD: Then we found out that there is activation of a signaling molecule called FLT3 in AML. This child also entered remission of leukemia after treatment with a high-dose FLT3 inhibitor [Quizartinib]. He is cured now.

I believe we are living in a very exciting era of precision medicine. We now have some magic bullets.

Dr. Anton Titov, MD: These are targeted, precise cancer medications. There is not only magic. There are also many problems with cancer treatment side effects.

It is very important not to make excessive promises. But I think the era where every child with cancer will be cured is certainly in the lifetime of a doctor who just now starts working in medicine.