Molecular Profiling

Molecular Profiling and Personalized Medicine

Molecular profiling has emerged to play a pivotal role in personalized medicine, classifying tumors based on genetic profiles for the purposes of cancer diagnosis or treatment,or predicting response to therapy. Innovative technologies, including next generation sequencing (NGS), can now clinically identify an extensive panel of actionable and exploratory genetic alterations.

In the US, Sarah Cannon physicians identify and order the most appropriate molecular test(s) from a number of “best in class” commercial laboratory service providers, such as Foundation Medicine or PathGroup accredited from the Commission on Laboratory Accreditation of the College of American Pathologists (CAP).  The NGS panels that are ordered target 35 to over 400 genes that are currently known to be altered in solid tumors or blood cancers. The appropriate molecular test and/or NGS panel is chosen based on tumor characteristics. 

In the UK, Sarah Cannon is working with University College London - Advanced Diagnostics (UCL-AD), a CPA-accredited molecular profiling laboratory, to develop novel technologies and assay menus and provide a clinical service to the private sector and the NHS, as well as a comprehensive research platform to the pharmaceutical industry.

With access to thousands of patients with different tumor types and access to the latest technologies used for molecular profiling, we are able to rapidly identify eligible patients for early and late-phase clinical trials and explore novel biomarkers that predict response to specific treatments.

No two cancers are identical. The genetic characteristics of a cancer vary from one patient to the next. So, even patients with the same type of cancer will respond differently to the same treatment, if their tumors have a different genetic makeup.

Sarah Cannon believes personalized medicine - with medical decisions and practices being tailored to the individual patient - is the way forward for cancer therapy and drug development. Several biological tests have emerged that help to define cancer subtypes and to predict treatment responses.

The development of molecular profiling technologies to assess DNA, RNA, protein and metabolites provides the opportunity to tailor medical care, both at tumor and patient levels. These approaches have the potential to fulfill the promise of delivering the right drug for the right indication to the right patient at the right time and as a result, form a core component of our ‘Personalized Medicine Initiative’.

Personalized therapy also offers the opportunity to increase therapeutic efficacy by targeting the genetic changes driving tumor behavior while at the same time decreasing inadvertent toxicity due to altered drug metabolism encoded by the patients’ genetic background.

Please find below answers to some commonly asked questions relating to the laboratory, the technology and/or the process or ordering tests/receiving reports:

  • What is personalized medicine and molecular profiling ?
  • What is next generation sequencing and why has the program adopted targeted next generation sequencing ?
  • What are the advantages of targeted next generation sequencing over single gene tests or multiple sequential single-gene tests ?

Personalized medicine is an emerging practice of medicine that uses an individual's genetic profile to guide decisions made in regard to the prevention, diagnosis, prognosis or treatment of disease. Personalized medicine for individuals with cancer uses the genetic profile of an individual's tumor to help clinicians select the appropriate medication or therapy and administer it using the proper dose or regimen.

Molecular profiling is an important facet of personalized medicine, and is the means by which tumors are classified. The genetic profiles are generated using a number of different tests/technologies, the results of which help guide diagnosis and predict response to therapy.

Next-generation sequencing (NGS), also known as high-throughput or massively parallel sequencing, is the catch-all term used to describe a number of different modern sequencing technologies. These recently developed technologies allow us to sequence large amounts of DNA and RNA much more quickly and cheaply than with the previously used Sanger sequencing approach, and as such have revolutionized the study of genomics and cancer biology. NGS provides a 'genetic survey' of a tissue sample by systematically identifying genetic alterations which - depending on the technology used and methods employed - can include single-nucleotide variants, insertions and deletions (indels), copy number variations, and large genomic rearrangements. Researchers and clinicians now utilize NGS to identify specific changes in DNA by rapidly and simultaneously sequencing multiple gene targets within multiple samples.

Currently, Sarah Cannon physicians are ordering targeted sequencing tests. In contrast to whole-genome, exome or whole-transcriptome sequencing, targeted DNA or RNA sequencing focuses the analysis on specific areas of interest. The ability to use targeted sequencing allows NGS to be employed routinely for genetic profiling of tumors in clinical practice and in clinical research. This sequencing approach can help identify rare or novel variants as well as those occurring at low frequency within a sample. When matched with germline DNA, it can also verify the somatic (tumor) nature rare variants across a large number of samples.

The main advantages of multi-gene testing using targeted next generation sequencing are as follows;

  • Tissue: Multiple genes can be tested from a single biopsy within one laboratory analysis. Less DNA/tissue is used in a multi-gene panel as compared to multiple single-gene tests; this is particularly pertinent to disease sub-types where tissue is limited
  • Time: It is quicker to conduct a single multi-gene test than multiple sequential single-gene tests
  • Cost: It is cheaper to conduct a single multi-gene test than multiple sequential single-gene tests
  • Information: NGS provides information regarding the relative frequency with which a mutation is found within a single biopsy; in turn, this information can be used to help inform clinical trial outcome data
  • Flexibility: As new genes are identified that are implicated in cancer, these can be added to NGS panels relatively quickly
  • Options: Multi-gene panel testing is increasingly required to guide patient selection to clinical trials, providing clinicians with more treatment options to offer their patients.

For more information on Sarah Cannon’s personalized medicine initiative, read the fact sheet here.