Penn Medicine

What is Personalized Diagnostics?

Cancer is personal. But cancer is also personal on another level, at the level of genomic signature traces in the DNA of its tumor cells.

Ultimately, cancer derives its power to grow from the information embedded in DNA sequence abnormalities—changes that occur only in the tumor tissue that instruct the cells in which these series of genetic abnormalities arise to grow and survive.

In an elaborate international scientific research project that began in the early 1990s, the Human Genome Project identified and mapped the approximately 20,000 to 25,000 genes in human DNA, and by 2001 had determined the sequences of the more than 6 billion chemical base pairs that make up the human genome.

By finding and studying the gene mutations in the human genome, cancer researchers and oncologists are able to pinpoint the information that will help to identify mutations important for associations with drug (chemotherapy) sensitivity, primary and secondary drug resistance, and tumor heterogeneity, with the goal to determine how these mutations would react to treatment options for each individual cancer patient. The CPD is using the vast accumulation of knowledge from this genomic research for use in the clinical setting here at the University of Pennsylvania.

Vast advances in computational power and biomedical informatics have now made it possible to extract the genetic make-up of each individual tumor and compare it against the scientific knowledge developed around the human genome project. The complete set of instructions that are encoded in the DNA sequences of tumor cells can now be determined "at once" by complex technologies that outline the genetic signatures through a technique called massively parallel sequencing.

This type of rapid sequencing has made it possible to identify a set of molecular changes and genomic signatures in the DNA of tumor cells that are distinct for each individual person—and that can reveal a genetic blueprint of the patient's tumor as discrete and singular as a fingerprint.

But much like a fingerprint, there are patterns, traces, and similarities that can be detected in tumors as well. These tumor mutations are blueprints that can be categorized according to their known similarities and subtypes. The blueprints, in turn, help to understand the underlying, common mutational architecture of a specific tumor, which can then be compared to what we know from the scientific knowledge generated through the human genome project.

This means that a single sequencing test can profile specific genomic arrangements that direct the malignant growth in your cells. The test results can then be compared to mutations that are scientifically known or common across all cancers and can be stratified or grouped into specific categories. In other words, a tumor can be identified according to known actionable and prognostic markers that have been found for your specific genetic blueprint.

What this means is a shift from a "generic" approach of what kind of cancer you may have by its location in the body, toward a specific understanding on the particular genetic subtype that characterizes your cancer. These identifying characteristics of your tumor can help guide you and your oncologist toward the appropriate treatment options for your particular cancer and assist in finding the care that manages your cancer best.

How Does Personalized Diagnostics Relate to Treatment?

Because these personal and specific mutation signatures can indicate whether and how a patient will respond to treatment, this kind of personalized diagnosis empowers physicians and patients to custom-tailor and individualize their treatment options accordingly.

Such highly specific diagnostic, therapeutic, and prognostic approaches are a crucial component of the move toward personalized medicine. Most cancer therapies are targeted at critical pathways of metabolic functions in the cell and knowing the genomic structure of your cancer makes it far easier to determine the options that are available for this particular tumor right away.

This kind of genomic diagnostic approach can identify particular patients who might benefit from current therapies, while sparing those who do not have a particular genetic signature from the costs and side effects of those therapies. Most important perhaps, it significantly reduces the time that conventional treatment approaches impose.

For a physician, knowing that a patient won't respond to a treatment is just as important as knowing that they will respond, removing the need for a "trial and error" drug regimen that can take between three and six months to generate meaningful knowledge.

In contrast, targeted genomic testing offers the hope that clinicians can devise the best treatment strategy at the time of diagnosis by cataloging the mutations that are driving tumor growth.

Will It Help?

Cancer typically occurs when the normal controls over cell growth stop working. This can be due to:

  • A mutation in a gene that signals a cell to divide, leading to uncontrolled growth (an oncogene)
  • The loss of a gene that normally tells a cell to stop dividing if something is wrong (a tumor suppressor)
  • A rearrangement that leads to the over-expression of a gene that prevents cell death (anti-apoptosis)
  • Mutations in DNA repair genes, that lead to accumulation of mutations (e.g. mismatch repair genes in colon cancer)
  • Other mutations with capabilities such as sustained angiogenesis, tissue invasion, and metastasis

The first question to discuss with your physician is whether or not this type of genomic testing is appropriate for you or your loved one and whether the information obtained will be useful.

To address these questions, it is important that you understand the nature of your cancer, how your particular type of cancer is treated, and what potential benefits of obtaining the mutation status of your tumor can yield.

Usually, there is no single mutation that is responsible for the changes that occur in a malignancy, but there are often one or a few "driver" mutations. But unless the tumor DNA is sequenced to specifically identify these mutations, there is no way to look at a tumor and know what mutations are present.

Depending on the type of cancer you have, there may be common or uncommon mutations associated with your cancer and specific drugs interacting with these targets may be available.

The benefit of these targeted agents is dependent on how critical the target was in the development of your cancer. In some instances, more than one target may need to be inhibited in order to achieve a response. It is also possible that the combination of a targeted therapy, in combination with traditional chemotherapy or radiation, may "tip the balance."

These are discussions you need to have with your oncologist to determine whether this knowledge would be beneficial to you and whether DNA sequencing can make your therapy as specific and effective as it can possibly be.

Useful Links

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Consult with your oncologist to determine whether DNA sequencing can make your therapy as specific and effective as it can possibly be.

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