The Molecular Barcode of Cancer — Targeting Treatment to Patient

Changes in DNA Underlie Cancer
Cancer develops when normal cells in the body grow and reproduce uncontrollably because of “mistakes” in the DNA code. DNA (a copy of which is contained in each cell) contains finely tuned instructions for cell growth and production, but as cells copy and pass on this DNA they sometimes make mistakes. These mistakes are technically called “mutations” and cause the DNA to be slightly different from the original.

The mutations that make cells grow too much and thereby cause cancer arise in the course of a person’s lifetime (as opposed to being a change in the DNA that the person is born with) and are called “somatic” mutations.

Editor’s note: Pending an FDA decision, 23andMe no longer offers new customers access to health reports referred to in this post. Customers who purchased prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will not. Those customers will have access to ancestry information as well as access to their uninterpreted raw data.

As far as disease names go, cancer appears to be pretty simple. Breast cancer is a cancer of the breast and prostate cancer is a cancer of the prostate. Although this naming system describes where the cancer starts out, it doesn’t tell us much about where the cancer will spread, which drugs (if any) will work, if the patient will have a bad reaction to a therapy, or whether the patient is likely to survive the cancer.

To understand these questions we need to drill deeper and analyze the molecular barcode of both the cancer and host.

Understanding the molecular profile of a cancer cell can help physicians understand which drugs will be effective in treating the cancer. The underlying code for what the cancer “shows” to the rest of the body and how it will behave in the body is in part dependent on the DNA inside the cancer cells. And what’s becoming evident is that cancer is much more complicated than we used to think.

Under each cancer umbrella there are actually many different rare diseases. Take breast cancer as an example. By most accounts there are four established subtypes, defined based on how the cancer “looks”, both as you would view it under a microscope and on the molecular level. For instance, a “HER2+” cancer displays the “Human Epidermal Growth Factor Receptor 2” (HER2) molecule on its surface but doesn’t display the estrogen receptor (ER) or progesterone receptor (PR), molecules that catch certain hormones as they pass by. Cancers that overexpress HER2 can be treated with specific drugs that target the HER2 molecule. But if a breast cancer is triple negative, meaning it doesn’t display any of these three receptors (HER, ER or PR), then drugs that target these molecules won’t be effective against the cancer.

The DNA that someone is born with differs in various places from person to person (so-called “germline” variation) and can also impact the course of treatment. Most clinical trials performed today do not incorporate genetic testing into the design of the trial. When they discover that some trial participants react poorly while others are super responders, they look to data points such as age, other diseases the patient is suffering from or medications he or she is taking. But it’s possible that the explanation lies deep down in the DNA — subtle differences in the barcode might be enough for some trial participants to develop an adverse reaction while other people taking the drug derive benefit without harm.

(See below to learn about a study by 23andMe and Genentech on how genes influence response to treatment for metastatic breast cancer).

Scientists are now learning more about different cancers by characterizing the mutations driving the tumor as well as a person’s own unique variants that he or she was born with. The course of cancer depends on both the signature of the tumor, something that stems from you but takes on its own life, and you — the host — a necessary participant in the fight against the cancer.

Research on the Genetics of Response to Treatment for Breast Cancer
23andMe and Genentech launched the InVite Study to understand how genes influence response to treatment for metastatic breast cancer. Potential findings of this study may help to determine if a person’s genes could play a role in response to bevacizumab, also known as Avastin. Participants are not expected to directly benefit from this study. View email for more information.

All 23andMe customers can participate in other scientific research through 23andMe’s research surveys. Not yet a customer? Visit our store or learn more!

  • Paul Appleton

    Read about your FDA Application…and others to come.
    I find your service valuable to me and have read alot of current medical literature
    about DTC.
    What is (I believe) critically important is that you not be cuckholded by treatment predictive info [or think you want to be in that realm]. You can “do no evil”, best by Gathering and delivering high utility information about high Odds Ratio- matched to your clients.., Risk Revising quantifications to add upon the CDC Family History….as your product/business model. …[ you could add value to your product by incentivizing your clients who complete the CDC "MyFamilyHistory" and fuse with the personal gene data you constantly revisit]…
    What public needs and wants ( and there never will be enough genetic counselors or educated PCPs) is useful, instantly current info of the rapidly moving field applied to prevention….. then needing to afford the “right” drug for “triple negative” will be a moot question.
    I hope you are accelerating the natural history of this paradigm shift….thank you.

  • Dave Mackey

    I love the work you guys are doing and am proud to be a customer of 23andMe, knowing that my support goes not only towards developing a great product for me personally but also towards medical advances that can help many worldwide. Keep up the great work!

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