Recurring or relapsed leukemia is a major treatment challenge. Leading pediatric cancer expert explains how genetic alterations in cancer cells help to use immunotherapy for leukemia treatment. Why fresh genomic sequencing of relapsed leukemia cells must be done? Any metastatic cancer must be sequenced. It is not wise to rely only on mutations discovered in the primary tumor. You also study genomics of leukemia progression in children. Dr. Anton Titov, MD. You identified some of the genomic markers of leukemia. They could serve as prognostic factors at the time of leukemia diagnosis. Dr. Shai Izraeli, MD. That helps obviously to stratify leukemia treatment. As you mentioned before, using molecular cancer markers can help to reduce the intensity of leukemia treatment. The goal is to lower the potential side effects and toxicity of cancer therapy in the long term. Relapse of leukemia is very tricky. We found a couple of mechanisms for relapse of leukemia. Dr. Anton Titov, MD. One of them is selection of mutations that provide resistance to cancer medications that we use. For example, I mentioned the discovery that we made in leukemia in patients with Down syndrome. This leukemia may be treated by a specific cancer medication. Dr. Shai Izraeli, MD. But we found that the leukemia relapse is often caused by the cancer cells that are resistant to this cancer medication. We need to find another way to treat relapsed leukemia. Dr. Anton Titov, MD. A molecular escape of child leukemia. A molecular escape, exactly! We identified several encouraging factors to treat child leukemia relapse. Up to 15% of leukemia cells at leukemia relapse are very genomically unstable. Dr. Anton Titov, MD. Why is this a potentially good finding? Because genetic instability of tumor is a valuable information in the age of precision medicine. Because in precision medicine we don't talk about a cancer medication that is specific to a disease. Dr. Shai Izraeli, MD. We use cancer medication that is specific to a genetic mutation or chromosome abnormality. For example, we found cancer medications that are called immune checkpoint inhibitors. When I saw “we”, I mean the pediatric leukemia scientific and medical community. The Nobel Prize was given this year for these cancer medications. Immune checkpoint inhibitors are effective especially for genomically unstable cancer cells. Dr. Anton Titov, MD. Why? Because genomically unstable cancer cells are recognized. But the normal immune system is weak. If you give cancer medications to encourage the normal immune system, they will attack these foreign cancer cells. We found several leukemia therapy options in this clinical trial that you mentioned. About 15% of all leukemic cells have this genomic instability phenotype. Dr. Shai Izraeli, MD. We call it mismatch repair genomic instability. Immune checkpoint inhibitors may be effective for some relapsed leukemias. It's also very important to study the genomics of relapsed leukemia. In childhood cancer in general, or in any cancer in general it is crucial information. Because the same abnormalities that existed in the beginning of cancer may not be present at the time of the cancer relapse. You have to think about targeted cancer therapy. We do need to know what is the genetic abnormality in the relapsed cancer. Because the genetics of the tumor shifts with time.There is a selective evolutionary pressure from the treatment. Dr. Anton Titov, MD. Genetic profile of the metastatic lesions changes from genetic mutations in the primary tumor. Precisely!
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