Diagnostics in Precision Medicine

The goal of precision medicine is to provide the right intervention at the right time to an individual patient. Diagnostic tests play a crucial role in the transformation away from one-size-fits-all medicine toward this new, personalized approach.


What is Precision Medicine?

Medications that are effective in some patients are useless, if not harmful, for others. Precision medicine is designed to segment patients based on their own biology, rather than treating patients based on population means. Medical decisions guided by the biology of the individual patient offer the promise of better outcomes.

Advances in personalized medicine are not confined to DNA analysis. A diverse set of diagnostic technologies are used to illuminate biology. Analyzing messenger RNA transcripts, the immediate downstream mediator of the genome, can detect gene expression in ways that analysis of the DNA itself cannot. Epigenetic changes to DNA can occur in response to environmental factors, and influence whether certain genes are turned on or off. Epigenetic factors have been linked to many health conditions, including heart disease, diabetes, and cancer. Scientists are working to standardize proteomic technologies such as mass spectrometry and proteins captured by modified aptamers, leading to more robust identification and measurement of protein biomarkers.

A New Treatment Paradigm


There are several mega-trends that have accelerated precision medicine in recent years.

  • Electronic medical records: Vast patient data are becoming available for analysis due to the widespread use of electronic medical records. Big Data analysis of aggregated EMR data, claims data and outcomes is enabling algorithm development and clinical insights linking outcomes and targeted treatments.
  • Reduced cost of sequencing: The reduction in cost for genomic analysis enables wider use of these technologies. The cost of sequencing a genome is ~$1,000 today, and projected to drop to <$100.
  • Unique partnerships: Technology companies such as Google and Apple are partnering with life sciences companies such as Illumina to capitalize on expertise in NGS sequencing, multi-omics, Big Data, machine-learning/artificial intelligence.


  • Reimbursement: Payors resist the new paradigm, partly because the evidence base is nascent for many applications, both diagnostic and treatment.
  • Regulatory: FDA procedures and classifications are out of sync with precision medicine principles. FDA currently approves cancer drugs at specific doses and based on the organ of origin. However, an analysis of a patient’s biomarkers may suggest that a cocktail of three different drugs — not necessarily used for that type of cancer before — would yield the patient’s best chance of beating the disease.
  • Education: Doctors need education on how to interpret the vast amounts of data to manage patients.

Precision Medicine in Oncology

As a fundamentally a genetic disorder, cancer is clearly the area in which the most progress has been made in precision medicine. According to the 2017 annual report from the Personalized Medicine Coalition, approximately 90% of the revenues for drugs that use companion diagnostics are in the oncology therapeutic area. The diagnostics are used predominantly for therapy selection and/or monitoring.


Cancer Statistics

According to the American Cancer Society:

  • Incidence: About 1.7 million new cancer cases are expected to be diagnosed in 2018.
  • Prevalence: More than 15.5 million Americans are cancer survivors as of January 1, 2016.
  • Deaths: About 609,640 Americans are expected to die of cancer in 2018.
  • Cost: Direct medical costs in 2015 were $80.2 billion (52% for outpatient, 38% inpatient care)

Novel Approaches to Oncology Medicines

The Tufts Center for the Study of Drug Development reports that f 42% of all therapies have the potential to be personalized medicines. In cancer, it’s 73%.  The Analysis Group reports that 85% of drugs in the oncology pipeline, including 79% in the clinical research phase, may be first-in-class medicines.

Percentage of Cancer Drug Development Projects that are Potentially Novel (2016)

The Role of Diagnostics

Many technologies are used for screening, diagnosis, prognosis, therapy selection and monitoring of cancer. Immunohistochemistry (IHC) has been a mainstay for staining proteins in tissue sections of tumors. Immunoassays are available to quantitate protein tumor markers in blood. FISH has been used to show chromosomal abnormalities.

Now, advanced molecular assays such as Next Generation Sequencing (NGS) have enabled scientists to identify mutations that are correlated with diseases and can direct effective treatments. As of March 1, 2018, there were 74,448 genetic tests marketed by CLIA-certified laboratories in the US. The majority are single-gene tests. Multi-gene panels, whole exome sequencing tests, and other complex testing products are growing.

As of March 1, 2018, there were 74,448 genetic tests marketed by CLIA-certified laboratories in the US.

Research tools used by academic and pharma scientists often evolve to diagnostic tests. Some follow a parallel regulatory path with the therapeutic and become companion diagnostics, while most are not tied to one drug and are marketed as complementary diagnostics.

Predictive Markers (Therapy Selection)

Diagnostic tests enable physicians to identify the most effective treatment by revealing specific molecular characteristics and prescribing medications targeted to the associated pathway. This often reduces costs and improves outcomes. One day, all cancer will be treated with a targeted course of treatment.

Originally FDA approved in 1998 for breast cancer, trastuzumab (Herceptin®) is the earliest example of a targeted biologic therapy paired with a companion diagnostic test. Approximately 30% of breast cancer cases are characterized by over-expression of the cell-surface protein HER2. Adding Herceptin to chemotherapy to treat patients with HER2+ tumors can reduce recurrence risk by 52%.

Treatments targeting genetic variants involved in the molecular pathway of disease, such as BRAF for melanoma, or ALK and EGFR targeted therapies for non-small cell lung cancer represent a remarkable improvement over trial-and-error medicine. Dozens of molecular assays are available to detect these mutations.

Prognostic Markers

Prognostic markers are used to risk stratify patients and indicate how a disease may develop. For example, Oncotype DX from Genomic Health is a multi-gene, mRNA assay that help physicians target the best course of treatment for breast cancer patients. It is indicated to determine whether breast cancer patient is likely to benefit from chemotherapy. The risk score informs physicians and patients on whether the cancer may be treated successfully with hormone therapy alone, or if the cost and side effects chemotherapy is warranted.

MDx Health, Agendia, Myriad, Genomic Health and others have developed a similar prognostic tests for prostate cancer and colon cancer. Numerous new prognostics biomarker tests are introduced regularly.


Liquid biopsy is an emerging class of cancer tests that may revolutionize both early detection and cancer treatment and recurrence monitoring. Liquid biopsy refers to a test done on a blood or urine sample to look for circulating tumor cells (CTCs) that are shed from tumors or for pieces of DNA from tumor cells (circulating tumor DNA, ctDNA or cell free DNA, cfDNA). A liquid biopsy may be used to help find cancer at an early stage, monitor treatment effectiveness or monitor for recurrence. Being able to take multiple samples of blood over time may also help doctors understand what kind of molecular changes are taking place in a tumor.

Marketed or under development liquid biopsy tests for oncology

Company Technology Application(s)
Abbott Detects aneuploidy for chromosomes 3, 7 and 17 and loss of the 9p21 locus in urine Bladder cancer
Aspira Labs (a Vermillion company) OVA1 test measures five ovarian cancer biomarkers Screen for ovarian cancer in patients with adnexal mass
Biocept Isolation and analysis of CTCs/ctDNA using real-time PCR Gastric, breast lung and other cancers
Chronix Biomedical Copy number instability index Identifying responders/non-responders
Cynvenio ClearID analyzes both CTC and ctDNA Breast cancer
Exosome Diagnostics Sequencing of exosomal RNA or DNA Prostate and lung cancer, solid tumors
Foundation Medicine NGS-based oncology panels Solid tumors; hematologic malignancies
Genomic Health ctDNA in urine Bladder cancer
Hologic PCA3/PSA RNA assay Prostate cancer
Inivatae 34 selected cancer-related genes Various cancers
Matritech NMP22 in urine Bladder cancer
MDxHealth Real-time quantitative PCR Urologic cancers
Myriad Genetics BRACAnalysisCDx CDx to direct treatment with Lynparza (olaparib) for advanced ovarian cancer
Onocyte Proprietary cancer markers and algorithm Lung and breast cancer
OPKO Health Prostate-specific kallikrein assay in blood Risk of aggressive prostate cancer
Pacific Edge 5 specific mRNA biomarkers in urine Bladder cancer
Personal Genome Diagnostics MYPG Comprehensive analysis of cancer genomes
RainDance RainDrop digital PCR instruments and consumables; sample prep for NGS Minimal residual disease in AML patients
Roche DNA sequencing Cancer (unspecified)
Trovagene Digital droplet polymerase chain reaction (ddPCR) CDx to detect mutations of BRAF, KRAS, EGFR to assist in choice of cancer therapy
Veracyte Percepta Bronchial Genomic Classifier Lung cancer

Bringing It All Together

  • Precision medicine segments patients based on their own molecular biology. Biomarker tests identify genetic or protein signatures to inform therapy selection, risk stratify patients or monitor disease.
  • Oncology has realized the most progress in applying precision medicine principles. These trends will continue. Companion and complementary diagnostics will be instrumental in future progress.

About the Author

Carrie Mulherin is CEO of Focus Marketing, offering consulting services in planning, market research, commercial execution and training to growing companies.

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