Monthly Archives: September 2015

For Cancer Patients, The Possibility Of DNA-Tailored Care

Holly Boehle looked at the expression on the face of her radiologist and knew something was wrong. Boehle had felt a lump just before the holidays and had decided to schedule a mammogram, even though she wasn’t due to start standard screening for another eight years. The mammogram was followed up with an ultrasound, and then a biopsy. Finally, she was given the formal diagnosis: invasive ductal carcinoma, the most common type of breast cancer.

The next week she traveled to Mayo Clinic’s oncology office in Rochester, Minn., where she met with clinical breast surgeon Dr. Judy Boughey who suggested Boehle consider participating in a new, ongoing study. She quickly agreed and became one of 140 women to take part in the Breast Cancer Genome-Guided Therapy Study, affectionately called “BEAUTY.”

By the end of the month, the first phase of the study was underway. Tumor tissue was taken from Boehle, and promptly brought into a lab where the sample was injected into mice with compromised immune systems. With her tumor tissue growing inside of them, the avatar mice are given different chemotherapy drugs in order to test the efficacy of treatment before they try it out on human Boehle.

BEAUTY’s Beginnings

Each patient in BEAUTY was given a biopsy, imaging, and chemotherapy treatment, followed by a second round of biopsy and imaging before they headed into the operating room. This gave researchers information on each patient’s blood and genetic makeup, and the sequencing information for their tumor before, during, and after chemotherapy treatment. The mouse avatars, known as patient xenografts, took up the patient’s individualized tumor 40 percent of the time, ultimately serving as a preview into the patient’s treatment outcome.

DNA Strand Free CCLicenseA class of chemo drug called taxanes are the standard of treatment for breast cancer, but doctors currently don’t have a genetic marker to indicate who will respond to taxane therapy and who won’t. That’s why anthracyclines and cyclophosphamide, a separate chemotherapy drug regimen, are typically given in conjunction as the first step in treatment followed by taxane therapy. However, Boughey’s team reversed the sequence for BEAUTY patients whose mice reacted well to the taxane treatment first. It turned out that those patients who responded best to the flipped treatment sequence also shared the same gene in their genetic makeup.

Based on how her mice reacted to treatment, Boehle was one of those patients who were treated with a reverse chemotherapy schedule than what the typical patient with invasive ductal carcinoma is treated with. Within six months of her diagnosis, Boehle’s tumor shrank considerably as a reaction to the chemotherapy.

Being part of the trial has long-term implications for Boehle, too. If the cancer were to recur, she says, “we would already know…what works for me and what doesn’t. It really opens up a whole new world for me and other breast cancer patients in terms of individualized medicine and knowing that I don’t need to be the person who they experiment on and say, ‘Let’s try this medication or chemotherapy and see if it works and we hope that it does.’”

Four years ago, when Boughey and her team began setting up the BEAUTY study, they wanted to be able to design a treatment plan with a relatively accessible patient population. Because breast cancer is so common among women, the research team chose to start work on individualized medicine with those patients with plans to eventually work their way to other solid tumor cancers such as prostate.

By sequencing the genome for both the tumor and the patient’s inheritable DNA, researchers are able to pull the curtain back and see what’s driving the tumor to grow, why it’s different from another tumor, and how the tumor might react to drug treatments. Harnessing the genetic sequence of a tumor in conjunction with a person’s DNA will allow doctors to expand personalized cancer treatments beyond breast cancer.

Standard of Care Tumor Sequencing

Sequencing a tumor for its complete genetic information can take as little as a few days, and as long as several weeks, depending upon the stage of cancer. Once they have the results, researchers then compare them to a patient’s individual germline cells, which contain hereditary mutations that occur during conception. Patients born with germline mutations can pass on to future generations. Somatic mutations can be caused by a number of different environmental factors and can occur spontaneously. As researchers unravel which gene mutations are responsible for causing each corresponding disease, it sets the foundation for creating individualized treatments through trial-and-error.

“From there potential drugs can be identified that act on genes and/or pathways,” Boughey and her colleague Dr. Matthew Goetz, a clinical oncologist at the Mayo Clinic, told Medical Daily in an email. “One novel aspect of the BEAUTY clinical trial is our ability to link drug response in the patients with both germline and somatic genomic information and validate using the patient derived xenografts [mouse avatars].”

Mayo Clinic’s research team is currently writing the protocol for BEAUTY 2 based on the types of tumors they identified, and the drug resistance and successes discovered in BEAUTY 1. Because they were able to prove mouse avatars, when administered the same drug that patients were treated with, mirror the drug response seen in patients, pharmaceutical companies will be involved with this next stage by designing medications based on study participants’ response to treatment.

BEAUTY, Boughey says, will “drive forward breast cancer treatments for the future.”

By Samantha Olson Displayed with permission from Medical DailyRePubHub Banner

 

 

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‘Second Cancers’ Are On The Rise, But It’s Kind Of A Good Thing

The number of “second cancer” patients, or individuals who develop two unrelated forms of cancer at different times in their lives, is on the rise. Although the news may sound grim, doctors say the increase is not due to patients’ poor health, but rather a sign that we’re getting better at detecting and beating cancer.

In the United States, nearly one in five new cases of cancer occur in individuals who have already had the disease. That’s a 300 percent increase since the 1970s, The Associated Press reported. While this figure may be startling, the fact remains that no matter what type of cancer a person has had, it’s possible to develop a new, unrelated cancer. According to the American Calab-test-tubes_227ncer Society, increasing numbers of second cancer cases are a sign that advances in early detection and treatment are saving an unprecedented amount of lives. In other words, people getting second cases of cancer means that more people than ever are actually surviving their first case.

Cancer is caused by mutations within the DNA that cause cells to no longer function correctly. These cells may eventually become cancerous. For some, the same mutations that led to the first cancer inevitably spur a second or even third case. This can occur even after the patient has made a full recovery. For example, doctors know women who have the BRCA1 mutation and have already experienced breast cancer are at a higher risk of developing an unrelated type of cancer, such as colon cancer. Because of this genetic risk, these patients will need to be monitored and screened for signs of other cancers for the remainder of their lives.

For others, the treatment that saved their life ends up being the reason their life is once again at risk. For example, although cancer treatments have become effective at destroying cancer without compromising the patient’s health, some treatments, such as radiation treatment, can actually give rise to new mutations and therefore new cancers.

Translational Science ResearchBattling cancer the second time can be trickier than the first because many treatments are ineffective or even deadly when given over a longer period of time.  Along with the medical limitations, experts agree that a second bout of cancer can be mentally difficult for patients to deal with. “I think it’s a lot tougher” for most people, Julia Rowland, director of the federal Office of Cancer Survivorship, told AP. “The first time you’re diagnosed, its fear of the unknown. When you have your next diagnosis, it’s fear of the known.”

Those who have survived past bouts of cancer need to be hypervigilant about cancer screening throughout their lives in order to ensure that if they do develop the disease again, they are able to detect it at the earliest possible stage. Although it may be daunting, patients should remember that cancer treatments are advancing on nearly a daily basis.

By Dana Dovey, Displayed with permission from Medical Daily
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