There are many tests which come under the umbrella of “personalized medicine.” Examples are molecular profiling, genetic testing, and chemosensitivity and chemoresistance testing. One of the goals of such tests is to help the patient’s medical team explore and evaluate potential treatment options. Some of the tests use tissue samples taken during a surgery, while others may require new samples to be obtained.
Each test may involve one or more different procedures. For example, molecular profiling is focused on identifying the genetic characteristics and “biomarkers” (genes, proteins and specific molecules) of a patient’s tumor and may involve various types of tests: immunohistochemistry (IHC tests), fluorescent in situ hybridization (FISH tests), and DNA sequencing to name a few. After a biomarker profile has been obtained, the results are compared with known data about treatments associated with the identified biomarkers. A report is then made to be shared with the oncology team to help guide the patient’s treatment plan. This “personalized medicine” approach will hopefully lead to targeted therapies which will, for the specific patient, be more effective, have fewer side effects, control the tumor growth and possibly cure the patient's cancer.
However, tests often have limitations on their usefulness. There is a lack of scientific results on the relationships between the mutations identified by molecular profiling and the activity of drugs supposedly related to these mutations. In vitro chemosensitivity and chemoresistance tests often lack the full range of agents that could be capable of inhibiting the identified targets. A number of sarcoma oncologists I have talked with believe the use of these tests is premature and the results cannot be used in the clinical setting. They state that in vitro chemosensitivity testing has been studied for more than two decades and has not been shown to reliably predict response to treatment.
The incredible amount of information being revealed by next generation sequencing does not appear to be leading directly to answers about treatment, but rather is revealing new degrees of complexity in sarcomas — within a patient’s own tumor and between tumors of the same type from different patients. This phenomena, which is referred to as tumor heterogeneity, poses important problems not only in the research setting, but in the clinical setting as well.
Tumor Heterogeneity's Impact on Testing, Research and Therapy
"Recent therapeutic advances in oncology have been driven by the identification of tumour genotype variations between patients, called interpatient heterogeneity, that predict the response of patients to targeted treatments. Subpopulations of cancer cells with unique genomes in the same patient may exist across different geographical regions of a tumour or evolve over time, called intratumour heterogeneity. Sequencing technologies can be used to characterize intratumour heterogeneity at diagnosis, monitor clonal dynamics during treatment and identify the emergence of clinical resistance during disease progression. Genetic interpatient and intratumour heterogeneity can pose challenges for the design of clinical trials that use these data." - From Tumour heterogeneity in the clinic by Bedard et al
"Developments in genomic techniques have provided insight into the remarkable genetic complexity of malignant tumours. There is increasing evidence that solid tumours may comprise of subpopulations of cells with distinct genomic alterations within the same tumour, a phenomenon termed intra-tumour heterogeneity. Intra-tumour heterogeneity is likely to have implications for cancer therapeutics and biomarker discovery, particularly in the era of targeted treatment, and evidence for a relationship between intra-tumoural heterogeneity and clinical outcome is emerging." - From Cancer heterogeneity: implications for targeted therapeutics by Fisher et al
"The heterogeneity that soft tissue sarcomas (STS) exhibit in their clinical behavior, even within histological subtypes, complicates patient care. Histological appearance is determined by gene expression. Morphologic features are generally good predictors of biologic behavior, however, metastatic propensity, tumor growth, and response to chemotherapy may be determined by gene expression patterns that do not correlate well with morphology." - From Identification of heterogeneity among soft tissue sarcomas... by Skubitz et al
"The problem of heterogeneity has long been appreciated among oncologists. Not only has intratumor genetic heterogeneity confounded targeted therapies, but intrapatient heterogeneity has also challenged interpretation of clinical trials. Advances in biomarker detection (protein, nucleic acid, metabolites, imaging signals), in combination with projects like The Cancer Genome Atlas (TCGA), Broad-Novartis Cancer Cell Line Encyclopedia, and patient-derived xenograft collections are helping cancer researchers quantify heterogeneity and determine its biological roles to shape therapeutic strategies." - From Tackling Cancer’s Heterogeneity in 2014... by Wuese and MacIvor:
At the Liddy Shriver Sarcoma Initiative, we often receive inquiries about molecular profiling, gene sequencing, chemosensitivity, etc. testing from patients and caregivers. We recommend that before patients have any of these tests that they discuss these approaches with their sarcoma team. Here are some questions we suggest patients ask:
- Do you recommended any of these tests to patients and, if not, why not?
- Which of these tests are appropriate for my type of sarcoma given the treatments that I have already undergone?
- What are the benefits of the tests for me?
- Will any of the tests reliably determine treatment options that I might respond to?
- Where should I get the tests done?
- What are the costs involved?
- How long does it take to get the results?
- Will insurance cover the tests?
- What are the risks involved?
- Who will help me understand the results of the tests?