Genomic profiling of tumors; Although standard protocols for chemotherapy still exist for each cancer, physicians
are aware that these protocols are only effective for a subset of patients. This issue has spawned the development
of many companies that examine the genes of your particular cancer. At AMT, we recommend this testing be performed
on tissue that has been resected, although the efficacy of this modality has been limited.
Benefits; Occasionally a mutation is found through genomic evaluation that reveals a
"driver" mutation, ie., a mutation that is spearheading the growth of the cancer.
Disadvantages; Although genomic evaluation of cancer tissue is commonly ordered by
oncologists, the success in improving survival has been modest. The Profiler Trial, a study in France of
1,944 patients with advanced cancer, looked at survival in patients who received targeted treatments based
on the genomic evaluation, vs. those who did not. At 3 years, 53.7% of patients who received the recommended
targeted therapy were alive, compared with 46.1% of patients who did not. The 5-year survival rate was also
higher for patients who received targeted therapy (34.8% vs 28.1%).
Whole cell cytometric profiling is a process whereby living cancer cells obtained from each patient
(via live tissue samples) actually are exposed to the broadest possible range of candidate chemotherapy drugs and
the true cell killing ability of each drug, that of which is precisely measured in real-time and in the presence of
each patient's own, living cancer cells. In addition, cytometric profiling clearly identifies the widely varying
difference in the susceptibility of each patient's cancer cells to different anti-cancer drugs within the same class
of drugs. Oncologists often see differences in patient response to different drugs which are thought to work via the
same general mechanism. Furthermore, this process measures the combined effect of all cellular gene and protein
interactions occurring within the cancer cell. Millions of these are known to occur but most are not yet identified
or fully-understood.
Finally, cytometric profiling also has the proven ability to identify synergy which frequently occurs in
rationally-selected drug combinations. Drugs which are only moderately active as single agents, sometimes becoming
extremely effective when combined with certain other agents. Cytometric profiling can pinpoint these drug
combinations. See Weisenthalcancer.com. Whenever
possible, sending living cancer cells, through either a fresh live tissue biopsy, or obtaining fluid from the
abdomen or lungs, is advised to optimize a treatment regimen.
Liquid Biopsy; We now have the ability to detect tumor mutations through a "liquid biopsy,"
meaning, through a blood draw. Most individuals with cancer have cell-free tumor DNA circulating in the bloodstream.
The genes of the DNA can be analyzed for mutations, similar to analyzing the genes from a piece of malignant tissue.
Why is a liquid biopsy necessary, especially if we already have looked at the gene mutations in the original tissue?
Cancer is a dynamic disease, which rapidly mutates, especially in response to treatment. The mutations that we see
in circulating tumor DNA (ctDNA) in the blood may be different from that which we saw on the original tissue biopsy.
These new mutations from a blood specimen represent the next generation of your cancer. If your previous cancer
treatment is no longer effective, a blood biopsy may reveal new mutations for which we can use a targeted drug, that
may be effective for your cancer. There are several labs that offer this service, such as Guardanthealth.com and Foundationmedicine.com.
Quantifying ctDNA; Signatera is a blood test that detects ctDNA. What is unique about this test, is
that they do whole genome sequencing of the primary tumor and somatic clonal variants are identified. Following
this, an assay of 16 tumor specific clonal somatic variants is generated, creating a specific tumor signature, for
that patient. The disease course is then monitored by quantifying the number of molecules/ml of ctDNA. This test can
be used in the following ways:
Evaluate the need for adjuvant chemotherapy following surgery, based on ctDNA.
Assess the response to treatment. Many cancers do not express tumor markers in the blood, so monitoring
ctDNA would be very helpful in these cases. Additionally, most patients with advanced disease get scanned
every 3 months; Signatera can be used to assess response to therapy in between scans.
Identify high risk patients with progressive disease who may benefit from early intervention or additional
imaging.
Detect molecular residual disease before it is even seen on imaging.
