March 06, 2020

Companion diagnostics bring precision to cancer treatment

By Cytiva

Targeted therapies are changing the face of cancer treatment, improving the outlook even for patients with difficult or advanced cancers. Companion diagnostics help physicians match the therapy to the patient’s cancer.

“You have an aggressive form of melanoma”

Hearing the word “aggressive” in a cancer diagnosis is shocking to any patient, but today precision medicine is providing targeted therapies that give better outcomes for many, even those dealing with difficult cancers. Companion diagnostics, developed alongside the targeted therapies, help physicians identify the patients who will benefit from a specific therapy.

Targeted cancer treatments for solid tumors

Cancer results from genetic mutations which cause tissue cells to divide and multiply rapidly. When developing a genomic-based therapy, researchers may use next-generation sequencing (NGS) to search for genetic mutations that are present only in the cancer cells, and then identify the biomarkers and target the cancer drug only to the cancer cells, avoiding damage to healthy tissue. The biomarker may be a genetic mutation, or a change in the proteins that are expressed by the cancer cells. Our growing understanding of individual cancer biomarkers underlies many of the recent advances in diagnosing and treating cancer.

Cancer biomarkers are found in a range of solid tumors, including melanoma, colorectal, breast, ovarian, and non-small cell lung cancer (NSCLC) and vary in form depending on disease pathway. While the mutations themselves can serve as genetic biomarkers, associated changes in cell behavior, characteristics, or protein expression can also act as biomarkers. The overexpression of certain receptors or proteins at the outer layer of a cancer cell is an example of a molecular biomarker.

Regardless of form, biomarkers can affect how cancer cells interacts with tumor surroundings. Biomarkers can influence a tumor’s response to therapy, or even give the cancer cell the ability to block immune recognition and attack. Biomarkers not only offer insight into mechanism of disease, they can also enable targeted therapies to deliver treatment to the cancer cells, while leaving normal cells unaffected.

There are two types of therapies that are targeted specifically to the patient’s tumor:

  • Treatments which enter the cancer cell and cause cell death.
  • Immunotherapy, which activates the patient’s own immune system to recognize and fight the cancer.

Both of these therapy types are based on understanding specific properties of the patient’s tumor at the molecular level, and using those attributes to target the tumor. Since each cancer is unique and individual, a treatment that works well for one patient’s melanoma, lung cancer or bladder cancer will not be effective for all cancers of that type. But for those for whom the therapy is a match, it can be a game-changer.

What is immunotherapy?

Immunotherapy refers to a group of anti-cancer drugs that are designed to use the patient’s own immune system to fight cancer. A common mechanism is to inhibit the PD-L1 immune checkpoint.

The programmed death 1 (PD-1) receptor is present on T cell surfaces to control T cell activity. When the PD-1 receptor interacts with the programmed death-ligand 1 (PD-L1) on other cell surfaces, the T cell is inactivated. Cancer cells can overly express PD-L1 and, in turn, bind to PD-1 receptors. This inactivates the T cell response, so that the cancer cells avoid detection and removal. Immunotherapy inhibits this checkpoint by using antibodies to bind either PD-L1 or PD-1. As a result, immune system activity can be maintained which leads to the destruction of cancer cells.

A number of immunotherapies, designed to target different parts of the immune checkpoint, have now been approved for the treatment of different cancers. Immunotherapies have shown some dramatic results in the treatment of advanced melanoma, turning it into a manageable disease in 50% of advanced melanoma patients (1). Immunotherapies are also being used for head and neck cancers, kidney cancer, bladder cancer, lymphoma and lung cancer.

Companion diagnostics: looking for the biomarkers

The biomarkers used in treatment development can also be used to identify tumors that will be susceptible to the therapy that targets that marker. Developed alongside a targeted cancer therapy, these companion diagnostics (CDx) may test for the specific genetic mutation, or for the overexpression of proteins that results from the mutation in order to identify patients who may benefit from the therapy. Companion diagnostics help understand a specific patient’s tumor and match them to a targeted drug or therapy.

  • Some companion diagnostics use next-generation sequencing (NGS) to test for the underlying genetic mutations of a tumor.
  • Another type of test identifies protein or molecular biomarkers which are present in the blood.
  • The microsatellite instability (MSI), tumor mutational burden (TMB), and PD-L1 tests look for markers that indicate immune checkpoint activation. These tests inform the clinician as to whether a patient is a suitable candidate for immunotherapy.

Interestingly, biomarkers can also help identify whether a drug commonly used to target a mutation in breast cancer, for instance, might be effective in treating a melanoma, due to the overexpression of the same receptor. A broad companion diagnostic (CDx) assay tests for multiple biomarkers to quickly identify the most appropriate treatment option for a patient. The companion diagnostic FoundationOne® CDx, which uses NGS, is the first broad companion diagnostic approved for all solid tumors.

Companion diagnostics help determine the best treatment to the patient’s cancer

CDx enables clinicians to give a specific therapy only to those for whom it will be effective. From the patient’s perspective, they can receive the treatment that is most likely to give a good result, while avoiding the possible side effects and expense of a therapy that will not be effective. Today there are over 30 companion diagnostic tests in commercial use.

When treating an aggressive cancer, time is of the essence. The ability to get the patient onto the most effective treatment immediately, as opposed to a hit-or-miss approach of trying various treatments, can be critical to survival and long-term outlook.

As solid-tissue NGS becomes more widely available, so too will other NGS-based companion diagnostics.

We support all aspects of the solid-tissue NGS workflow. For more specific support, with any type of NGS workflow, please contact our Life Sciences support team.


  1. Eggermont, A. et al. Combination Immunotherapy Development in Melanoma. ASCO Educational Book 38, 197-207 (2018).