January 27, 2018
Igor F. Tsigelny, Ph.D., Co-founder and Chief Strategic Officer at CureMatch® and research professor at University of California, San Diego, is a co-author of “Genomic landscape of cell-free DNA in patients with colorectal cancer” in Cancer Discovery along with group of colleagues from Duke University Medical Center, University of Texas MD Anderson Cancer Center, Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, Caris Life Sciences, and Guardant Health, Inc. organized by the Drs. Ryan B. Corcoran and Scott Kopetz. This study represents one of the largest-scale research projects comparing genomic profiling of cfDNA versus direct tumor sequencing.
The current Cancer Discovery article highlights how liquid biopsy techniques, which apply genomic sequencing of circulating DNA isolated from a small vial of blood, can effectively detect cellular mutations in colorectal cancer (CRC) patients. For the study, cell-free DNA (cfDNA) was collected via liquid biopsies from 1,397 CRC patients and the genomic information was compared to three independent tissue-based sequencing summaries. It was found that the liquid biopsy approach detects genomic alterations at frequencies comparable to those observed by direct tumor sequencing. Furthermore, the cfDNA also identified new mutations and offered insights into tumor therapeutic resistance.
The results of the study suggest that cfDNA profiling can effectively define the genomic landscape of cancer and yield important biologic insights. This is very significant because liquid biopsies can identify potentially important genomic alterations in patients for whom traditional biopsies may be difficult in terms of risk or cost. The blood test is relatively non-invasive and inexpensive when compared with tissue biopsy and facilitates the collection of multiple specimens over time, something that is challenging to do with tissue biopsy.
Both oncologists and their patients like the idea of a non-invasive test to monitor cancer. Cell-free DNA testing can identify mechanisms of resistance as well as future treatment options. The cfDNA test in conjunction with computational modeling can be used to adjust therapy as appropriate for those patients progressing after initial treatment. Biopsy-free testing accelerates clinical research and transforms precision medicine.
Genetic mutation discoveries lead directly to personalized medicine options. Selection of cancer drugs is the next step after genomic sequencing. This requires a clear understanding of the possible impacts of known aberrations to activity and drug resistance of the affected genes. In the Cancer Discovery article, Dr. Tsigelny theoretically elucidated functional changes of protein EGFR resistance to drugs caused by the specific mutations.
“One of the first and major steps in precision medicine is elucidation of functional impacts of gene aberrations. Such information sometimes exists in publications, but in the vast majority of cases, it does not. Thus, one needs to use computational modeling and simulations to predict possible gene activation or inhibition leading to deleterious effects and determine which mutations lead to an increased resistance to known drugs. When such work is done, the next steps are straightforward,” states Dr. Tsigelny.
Research shows that genetic markers of cancer offer some of the best indicators to recommend personalized treatments and improve survival rates. Identification of specific genetic mutations can provide oncologists with the critical information necessary to effectively recommend therapeutic strategies that overcome resistance mechanisms. As the genomic landscape of oncology is being established, researchers such as Tsigelny are offering breakthroughs for oncologists with practical technological applications.
Dr. Tsigelny is one of the major developers of the CureMatch computational system which utilizes proprietary algorithms to distill over 4.5 million combinations of commonly-used as well as newly approved cancer treatments found in massive pharmacological and clinical archives into actionable intelligence for oncologists. CureMatch is an evidence-based precision medicine system which enables oncologists to offer Personalized Combination Therapy® options to their patients.
A cancer patient’s tumor profiling data is required to use CureMatch, either tissue or cfDNA. The mutations that are specific to each individual patient’s cancer are identified, and the CureMatch computational analysis generates a PreciGENE Score which reflects the degree to which a therapy or combination of therapies matches a patient’s biomarker profile. It is represented by a percentage and may be used to compare potential treatment regimens. Determining the synergisms of oncology drugs allows potential mono-therapies, two-drug combinations, and three-drug combinations to be scored and ranked to target specific molecular aberrations.
“The growing field of genomics is driving personalized medicine for cancer care, and Igor F. Tsigelny is a biomedical researcher advancing intelligent computing systems to assist oncologists,” stated Stephane Richard Ph.D., CureMatch President and CEO.