Cancer by nature is about change. Cancer cells multiply and evolve quickly. Certain types of brain tumors called gliomas pose their own particular challenges, as an initial tumor’s genetic makeup might be very different from that of a recurrent tumor. Further understanding of this could have great implications on future management of these recurrent and more aggressive tumors.
In the December 12, 2013 issue of Science Express neurosurgery researchers from the University of California San Francisco investigated the genetic makeup of both initial and recurrent tumors and compared the mutations found in each. They also evaluated how treatment with the widely used chemotherapeutic drug temozolomide (TMZ) might affect the evolution into a secondary tumor.
Low-grade gliomas are usually treated through observation, surgical removal, chemotherapy, radiation, or some combination of these options. Frequently these tumors return, sometimes years later, in a more aggressive and less treatable form. TMZ works quite effectively on original gliomas but has shown little success in recurrent tumors which usually have a grim prognosis.
In most cancers, recurrent tumors grow in different locations in the body yet share common genetics. In the case of the gliomas, new tumors appear in nearly the same location as the original tumors but the genetic profiles of the two are quite distinct. It is hypothesized that the new tumors grow from tissue left behind from the original surgical excision and then progress on their own distinct evolutionary path.
To test this hypothesis, tissue samples were taken from 23 patients’ original and secondary tumors. Genetic sequencing determined that in 43% of the cases, only about half of the mutations from the original tumors were present in the recurrent tumors. These results diverged from previous research showing that tumor evolution generally progresses along the same genetic path. This is known as clonal evolution.
Additionally, in 6 of the 10 samples from patients treated with TMZ, it was found that the number of mutations in the recurrent tumor was approximately 30 times greater than expected. These results suggested that TMZ treatment was the cause for the newer mutations in the tumor and was responsible for the change from low-grade glioma to higher grade glioma.
The results of this research will lay the foundation for future testing to determine if particular genes contributing to the TMZ-induced hypermutations could be turned off, allowing for the benefits of TMZ treatment without the deadly mutational side effects.
Precision medicine’s goal is to use information specific to each patient’s disease when making treatment decisions. This study moves us one step closer to that goal for patients with glioma.
{Glioma Facebook post}
Is your chemotherapy drug causing your tumor to grow faster? UCSF researchers describe their new understanding of tumor evolution, and their surprising discovery on how TMZ might affect recurrent gliomas.
science.sciencemag.org/content/343/6167/189.full
{Glioma Tweet}
UCSF research finds therapies drive mutations in recurrent gliomas. @sciencemagazine http://bit.ly/2rRtyWp #ucsfneuro #PrecisionMedicine
In the December 12, 2013 issue of Science Express neurosurgery researchers from the University of California San Francisco investigated the genetic makeup of both initial and recurrent tumors and compared the mutations found in each. They also evaluated how treatment with the widely used chemotherapeutic drug temozolomide (TMZ) might affect the evolution into a secondary tumor.
Low-grade gliomas are usually treated through observation, surgical removal, chemotherapy, radiation, or some combination of these options. Frequently these tumors return, sometimes years later, in a more aggressive and less treatable form. TMZ works quite effectively on original gliomas but has shown little success in recurrent tumors which usually have a grim prognosis.
In most cancers, recurrent tumors grow in different locations in the body yet share common genetics. In the case of the gliomas, new tumors appear in nearly the same location as the original tumors but the genetic profiles of the two are quite distinct. It is hypothesized that the new tumors grow from tissue left behind from the original surgical excision and then progress on their own distinct evolutionary path.
To test this hypothesis, tissue samples were taken from 23 patients’ original and secondary tumors. Genetic sequencing determined that in 43% of the cases, only about half of the mutations from the original tumors were present in the recurrent tumors. These results diverged from previous research showing that tumor evolution generally progresses along the same genetic path. This is known as clonal evolution.
Additionally, in 6 of the 10 samples from patients treated with TMZ, it was found that the number of mutations in the recurrent tumor was approximately 30 times greater than expected. These results suggested that TMZ treatment was the cause for the newer mutations in the tumor and was responsible for the change from low-grade glioma to higher grade glioma.
The results of this research will lay the foundation for future testing to determine if particular genes contributing to the TMZ-induced hypermutations could be turned off, allowing for the benefits of TMZ treatment without the deadly mutational side effects.
Precision medicine’s goal is to use information specific to each patient’s disease when making treatment decisions. This study moves us one step closer to that goal for patients with glioma.
{Glioma Facebook post}
Is your chemotherapy drug causing your tumor to grow faster? UCSF researchers describe their new understanding of tumor evolution, and their surprising discovery on how TMZ might affect recurrent gliomas.
science.sciencemag.org/content/343/6167/189.full
{Glioma Tweet}
UCSF research finds therapies drive mutations in recurrent gliomas. @sciencemagazine http://bit.ly/2rRtyWp #ucsfneuro #PrecisionMedicine