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Human Tumor Sequencing
Identifying associations between patient’s DNA and response to cancer therapy
A newly diagnosed cancer patient’s prognosis and treatment plan today are primarily guided by the stage and grade of the patient’s primary tumor. While the tumor’s stage is based on the extent of the cancer in the body, its grade represents how abnormal the cancer cells appear under a microscope.
In the future, the tumor’s DNA signature will be as important as stage and grade and will allow physicians to tailor the prognosis and therapy according to the genetic profile of the patient’s cancer. To accelerate the pace of research to unravel the genetic complexities of cancer and to translate that knowledge to patient care, the Scripps Translational Science Institute (STSI) created the Human Tumor Sequencing Protocol (HUTS).
Cancers are genetically complex, because even people with the same form of cancer do not have the same DNA mutations in their tumors. Even within a single tumor, the malignant cells can be genetically different.
In addition, only a relatively few of a malignant cell’s thousands of DNA mistakes drive the growth and spread of the cancer. The remainder, the “passenger” mutations, is a byproduct of the cancer cells’ reduced ability to resist mutation in its DNA and is likely unrelated to cancer cell development. Distinguishing the “driver” from the “passenger” mutations enables STSI researchers and other scientists to identify the biological pathways that should be targeted when individualizing a cancer patient’s therapy.
With each cancer patient who volunteers for HUTS, STSI’s approach is “N-of-1”: the patient is monitored as if he/she is participating in a clinical trial evaluating each of the therapeutic regimens prescribed by the patient’s oncologist as part of the process to define the optimal treatment strategy. However, unlike a conventional clinical trial, the “N-of-1” approach searches for associations between a patient’s genetic factors and the effectiveness and safety of each prescribed therapy.
If biomarkers useful in predicting disease progression or response to therapeutics are identified, STSI scientists collaborate with the patient’s oncologist to help interpret the results.
STSI’s genomic analysis of each tumor is shared with the patient and his/her physician, with the understanding that the likelihood that the findings will directly benefit the patient now is minimal. It will be future patients for whom the research will have the most impact.
For more information:
In the scientific journal Cancer Research, STSI scientists in 2008 described a method of predicting driver cancer cell mutations in protein kinases:
http://cancerres.aacrjournals.org/content/68/6/1675.full.pdf+html
“Scripps Health Begins Pioneering Study of Human Tumor Sequencing in Cancer Patients,” Feb. 17, 2010 news release:
http://www.scripps.org/news_items/3613-scripps-health-begins-pioneering-study-of-human-tumor-sequencing-in-cancer-patients
