Scientists are studying cancer genomes to more precisely diagnose their patients' diseases - offering hope for targeted drug treatments.
Next, he recalls, he felt ushered into “the jaws of the medical system very quickly.” He spent a couple of days meeting with a team of doctors at Beth Israel Deaconess Medical Center in nearby Boston. One of them was from a medical field he hadn’t even known existed, a pulmonary interventionist, who would perform a biopsy on the mass in his lung.
“Knowing there was a medicine for my particular type of cancer was like a weight lifted off my shoulders."
A week later he and his wife Allison returned to meet with the oncologist, radiologist, pulmonary interventionist – his medical team. They confirmed his initial diagnosis: Stage 4 metastatic lung cancer that had spread to several parts of his body. “We just sat there, stunned,” he says. “I felt like I was getting hit by a wrecking ball over and over.”
An onslaught of medical terminology about what they had identified flowed over the shocked couple, but then the medical team switched gears, he recalls. They offered hope. “They told me, ‘Hey, you’re not a smoker, so that’s good,’” Reiner says. “‘There’s a good chance that what’s driving this disease for you is actually a genetic mutation, and we have ways to understand more about what that could be through some simple testing.’”
They told him about Foundation Medicine, a company launched in neighboring Cambridge, MA, in 2009 that develops, manufactures, and sells genomic profiling assays. These are tests that, according to the company’s website, “can analyze a broad panel of genes to detect the four main classes of genomic alterations known to drive cancer growth.” With these insights, certain patients can be matched with therapies targeted specifically for the genetic driver(s) of their cancer. The company maintains one of the largest cancer genomic databases in the world, with more than 500,000 patient samples profiled, and they have more than 65 biopharma partners.
According to Foundation Medicine, they are the only company that has FDA-approved tests for both tissue- and blood-based comprehensive genomic profiling tests. One other company has an FDA-approved biopsy test, and several other companies offer tissue-based genomic profiling. Additionally, several major cancer centers like Memorial Sloan Kettering in New York and Anderson Cancer Center in Texas have their own such testing platforms.
Currently, genomic profiling is more accessible for patients with advanced cancer, due to broader insurance coverage in later stages of disease.
“Right now, the vast majority of patients either have cancers for which we don’t have treatments or they have genetic alterations that are not known,” says Jorge Garcia, MD, Division Chief, Solid Tumor Oncology, UH Cleveland Medical Center, which has its own CGP testing platform. “However, a significant proportion of patients with advanced cancer have alterations that we can tap for therapeutic purposes.”
Foundation Medicine estimates that in 2017, just over 5 percent of advanced solid cancer patients in the U.S. received CGP testing. In 2021, they estimate that number is between 25 to 30 percent of advanced solid cancer patients in the U.S., which doesn’t include patients who are tested with small (less than 50 genes) panels. Their panel tests for more than 300 cancer-related genes.
“The good news is the platforms we are developing are better and more comprehensive, and they’re going to continue to be larger data sets,” Dr. Garcia adds.
In Reiner’s case, his team ordered comprehensive genetic profiling on both his tissue and blood, from Foundation Medicine.
At this point, Reiner still wasn’t sure what genetic mutations were or how they factored into cancer or what comprehensive genomic profiling entailed. That day, though, his team ushered the Reiners into the world of precision oncology that placed him on much more sure footing to learn about and fight the specific lung cancer that had been troubling him for more than a year.
What genetic alterations were driving his cancer? Foundation Medicine’s tests were about to find out.
At the core of these tests is next generation sequencing, a DNA sequencing technology. Since 2009, this has revolutionized genomic research, according to the National Center for Biotechnology Information, because it allows an entire human genome to be sequenced within one day. Cancer genomics posits that cancer is caused by mutations and is a disease of the genome. Now, cancer genomes can be systemically studied in their entirety. For cancer patients such as Reiner, NGS can provide a more precise diagnosis and classification of the disease, more accurate prognosis, and potentially the identification of targeted drug treatments. Ultimately, the technology can provide the basis of personalized cancer management.
The detailed reports supply patients and their oncologists with extensive information about the patient’s genomic profile and potential treatment options that they can discuss together. Reiner trusted his doctors that this approach was worth the two- or three-week wait to receive the Foundation Medicine report and the specifically targeted treatment, rather than immediately jump into a round of chemotherapy. He is especially grateful now, he says, because the report delivered a great deal of relief from his previously exhausting and growing anxiety about having cancer.
Reiner and his team learned his lung cancer contained the epidermal growth factor receptor (EGFR) mutation. That biomarker enabled his oncologist to prescribe Tagrisso (osimertinib), a medication developed to directly target that genetic mutation.
“Knowing there was a medicine for my particular type of cancer was like a weight lifted off my shoulders,” he says. “It only took a week or two before my cough finally started subsiding. This pill goes right after the particular piece of genetic material in the tumor that’s causing its growth.”
Dr. Jerry Mitchell, director field medical oncology, Foundation Medicine, in Columbus, Ohio, explains that genomic profiling is generating substantial impacts today. “This is a technology that is the standard of care across many advanced malignancies that takes patients from chemotherapy-only options to very targeted options or immunotherapy options,” he says. “You can also look at complex biomarkers, and these are not specific genetic changes but different genes across the tumor to get a biomarker.”
According to Dr. Mitchell, Foundation Medicine’s technology can test more than 324 different cancer-related genes in a single test. Thus, a growing number of patients are benefitting from comprehensive genetic profiling, due to the rapidly growing number of targeted therapies. While not all of the cancers are treatable yet, the company uses that information to partner with researchers to find new potential therapies for patient groups that may have rare mutations.
Since his tumor’s diagnosis, Reiner has undergone chemotherapy and a couple surgeries to treat the metastatic cancer in other parts of his body, but the drug Tagrisso has significantly reduced his lung tumor. Now, having learned so much during the past couple of years, he is grateful for precision oncology. He still reflects on the probability that, had the Tagrisso pill not been available in May 2019, he might have only survived for another six months or a year.
“Comprehensive Genomic Profiling is not some future state, but in both the U.S. and Europe, it is a very standard, accepted, and recommended first step to knowing how to treat your cancer,” says Dr. Mitchell, adding that he feels fortunate to be an oncologist in this era. “However, we know there are still people not getting this recommended testing, so we still have opportunities to find many more patients and impact them by knowing the molecular profile of their cancer.”
Marielle Gross, a professor at the University of Pittsburgh, shows patients a new app that tracks how their samples are used during biomedical research.
Tissue donors can track what scientists do with their samples while safeguarding privacy, through a pilot program initiated in October by researchers at the Johns Hopkins Berman Institute of Bioethics and the University of Pittsburgh’s Institute for Precision Medicine. The program uses blockchain technology to offer patients this opportunity through the University of Pittsburgh's Breast Disease Research Repository, while assuring that their identities remain anonymous to investigators.
A blockchain is a digital, tamper-proof ledger of transactions duplicated and distributed across a computer system network. Whenever a transaction occurs with a patient’s sample, multiple stakeholders can track it while the owner’s identity remains encrypted. Special certificates called “nonfungible tokens,” or NFTs, represent patients’ unique samples on a trusted and widely used blockchain that reinforces transparency.
Blockchain could be used to notify people if cancer researchers discover that they have certain risk factors.
“Healthcare is very data rich, but control of that data often does not lie with the patient,” said Julius Bogdan, vice president of analytics for North America at the Healthcare Information and Management Systems Society (HIMSS), a Chicago-based global technology nonprofit. “NFTs allow for the encapsulation of a patient’s data in a digital asset controlled by the patient.” He added that this technology enables a more secure and informed method of participating in clinical and research trials.
Without this technology, de-identification of patients’ samples during biomedical research had the unintended consequence of preventing them from discovering what researchers find -- even if that data could benefit their health. A solution was urgently needed, said Marielle Gross, assistant professor of obstetrics, gynecology and reproductive science and bioethics at the University of Pittsburgh School of Medicine.
“A researcher can learn something from your bio samples or medical records that could be life-saving information for you, and they have no way to let you or your doctor know,” said Gross, who is also an affiliate assistant professor at the Berman Institute. “There’s no good reason for that to stay the way that it is.”
For instance, blockchain could be used to notify people if cancer researchers discover that they have certain risk factors. Gross estimated that less than half of breast cancer patients are tested for mutations in BRCA1 and BRCA2 — tumor suppressor genes that are important in combating cancer. With normal function, these genes help prevent breast, ovarian and other cells from proliferating in an uncontrolled manner. If researchers find mutations, it’s relevant for a patient’s and family’s follow-up care — and that’s a prime example of how this newly designed app could play a life-saving role, she said.
Liz Burton was one of the first patients at the University of Pittsburgh to opt for the app -- called de-bi, which is short for decentralized biobank -- before undergoing a mastectomy for early-stage breast cancer in November, after it was diagnosed on a routine mammogram. She often takes part in medical research and looks forward to tracking her tissues.
“Anytime there’s a scientific experiment or study, I’m quick to participate -- to advance my own wellness as well as knowledge in general,” said Burton, 49, a life insurance service representative who lives in Carnegie, Pa. “It’s my way of contributing.”
Liz Burton was one of the first patients at the University of Pittsburgh to opt for the app before undergoing a mastectomy for early-stage breast cancer.
Liz Burton
The pilot program raises the issue of what investigators may owe study participants, especially since certain populations, such as Black and indigenous peoples, historically were not treated in an ethical manner for scientific purposes. “It’s a truly laudable effort,” Tamar Schiff, a postdoctoral fellow in medical ethics at New York University’s Grossman School of Medicine, said of the endeavor. “Research participants are beautifully altruistic.”
Lauren Sankary, a bioethicist and associate director of the neuroethics program at Cleveland Clinic, agrees that the pilot program provides increased transparency for study participants regarding how scientists use their tissues while acknowledging individuals’ contributions to research.
However, she added, “it may require researchers to develop a process for ongoing communication to be responsive to additional input from research participants.”
Peter H. Schwartz, professor of medicine and director of Indiana University’s Center for Bioethics in Indianapolis, said the program is promising, but he wonders what will happen if a patient has concerns about a particular research project involving their tissues.
“I can imagine a situation where a patient objects to their sample being used for some disease they’ve never heard about, or which carries some kind of stigma like a mental illness,” Schwartz said, noting that researchers would have to evaluate how to react. “There’s no simple answer to those questions, but the technology has to be assessed with an eye to the problems it could raise.”
To truly make a difference, blockchain must enable broad consent from patients, not just de-identification.
As a result, researchers may need to factor in how much information to share with patients and how to explain it, Schiff said. There are also concerns that in tracking their samples, patients could tell others what they learned before researchers are ready to publicly release this information. However, Bogdan, the vice president of the HIMSS nonprofit, believes only a minimal study identifier would be stored in an NFT, not patient data, research results or any type of proprietary trial information.
Some patients may be confused by blockchain and reluctant to embrace it. “The complexity of NFTs may prevent the average citizen from capitalizing on their potential or vendors willing to participate in the blockchain network,” Bogdan said. “Blockchain technology is also quite costly in terms of computational power and energy consumption, contributing to greenhouse gas emissions and climate change.”
In addition, this nascent, groundbreaking technology is immature and vulnerable to data security flaws, disputes over intellectual property rights and privacy issues, though it does offer baseline protections to maintain confidentiality. To truly make a difference, blockchain must enable broad consent from patients, not just de-identification, said Robyn Shapiro, a bioethicist and founding attorney at Health Sciences Law Group near Milwaukee.
The Henrietta Lacks story is a prime example, Shapiro noted. During her treatment for cervical cancer at Johns Hopkins, Lacks’s tissue was de-identified (albeit not entirely, because her cell line, HeLa, bore her initials). After her death, those cells were replicated and distributed for important and lucrative research and product development purposes without her knowledge or consent.
Nonetheless, Shapiro thinks that the initiative by the University of Pittsburgh and Johns Hopkins has potential to solve some ethical challenges involved in research use of biospecimens. “Compared to the system that allowed Lacks’s cells to be used without her permission, Shapiro said, “blockchain technology using nonfungible tokens that allow patients to follow their samples may enhance transparency, accountability and respect for persons who contribute their tissue and clinical data for research.”
Read more about laws that have prevented people from the rights to their own cells.