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Ending cancer requires personalization. At MD Anderson, the promise of personalized medicine is emerging in new and exciting ways, thanks to our efforts to accelerate scientific innovation and translate discoveries into meaningful patient outcomes.
Breakthroughs in cancer medicine, after all, rely on more than the researcher, clinician or institution. Patients are active and critical participants in their own prognoses and treatments, from their ability to discuss symptoms and risk factors to the complete assessment of individual genome variation, which now can be discerned. We are discovering, more and more, that cancer fundamentally is a disease of the genome — it derives, subsists and remains encoded within the DNA, molecules and cells that make each patient unique.
This is a primary reason two patients receiving similar treatments for the same type of tumor often experience different disease trajectories. When two patients with chronic myeloid leukemia, for example, are given a tablet that delivers chemotherapy, one may experience fatigue, gastrointestinal distress and swelling in the legs while the other may experience no side effects.
Why do immunotherapies fail to have a significant clinical response in the vast majority of patients? Why do tumors develop resistance to therapy over time? Most important, how can we stop this?
“We have to look at cancer treatment in a new way, and with new depth, and it’s going to be an ongoing interrogation of our systems, down to the last molecule,” says Andrew Futreal, Ph.D., chair of Genomic Medicine. “We’re seeing a transformative shift in health care where the patient, and all the information they possess, is a critical partner in their own treatment strategy, and we need new approaches and technologies to gather that information and meet this need.”
Our new approach is MD Anderson Patient Mosaic™, a landmark research effort and institutional priority program seeking a comprehensive view of cancer at the individual patient level. Led by Futreal, Patient Mosaic™ assembles the many shards, strands and bits of data associated with cancer risk and progression, from intake information and history to deep genetic sequencing and profiling data of the patient and the tumor microenvironment.
Institutional researchers classify this data, building large-scale assessments by visualizing minute points of variance across everything from disease type to genetic composition of the patient’s immune system. From all this, an image emerges — a rich diagnostic and potentially curative collage brushed generously with deep hues of data, observation and analysis by the pre-eminent scientific expertise associated with the No. 1 comprehensive cancer center in the world.
Scheduled for full launch in summer 2021, the program will identify, obtain consent from and enroll 10,000 MD Anderson patients receiving standard-of-care immunotherapies, molecularly targeted therapies and chemotherapies, including pediatric patients and patients undergoing treatment for rare tumors. Patient Mosaic will sequence and analyze both tumor-derived and patient-derived genetic material from these participants.
One operational function that sets this program apart is its ability to collaborate with a wide-ranging roster of faculty researchers to measure broadly and profoundly, applying thorough examination of the genetic composition of the patient’s immune system and microbiome — the latter an intricate and diverse community of bacteria, fungi and viruses affecting everything from how we process food to how we potentially would respond to different cancer treatments. Critical to this deep measurement, what drives this program to broad analytical potential, is our unique ability to include patient-reported outcomes data (e.g., symptoms, nutrition and activity tracker information) gathered repeatedly and throughout the full course of a patient’s care, starting the moment treatment begins.
MD Anderson is the only institution equipped to launch such a patient-based, data-driven program of this magnitude and potential impact. While our experience and expertise will foster Patient Mosaic as a significant, institution-wide research initiative, our patient volume is the real differentiator. In Fiscal Year 2020, more than 151,000 people sought MD Anderson’s superior care and services. We enrolled over 8,200 patients in more than 1,400 clinical trials. Our patient volume provides innumerable data points from which we will build the clear, definitive and personalized image of cancer’s various forms.
Additionally, thanks to multiple progress-enabling research platforms that MD Anderson’s Moon Shots Program® made possible, Patient Mosaic uses established data generation, integration and analysis systems to capture all the lessons learned from each patient who receives care. Our unique research infrastructure enables physician-scientists to integrate leading-edge basic immunology with novel clinical trials to gain information for the treatment and eradication of all types of cancer, as well as develop immunologic data for integration. And this collaborative network streamlines transfer of high-quality, appropriately processed and well-characterized specimens for analysis via the Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO) platform.
“Cancer is a convoluted system, acting more like a collection of species with different levels of activity and behaviors. All of these factors, orbiting and interacting as cancer progresses, are what drive treatment resistance, refractory disease and risk,” Futreal says. “And because we treat, to the best of our ability, one patient with one tumor type in a similar way as the next patient with the same tumor type, and continue to see different results, we must conclude that the key to unlocking cancer’s complexity lies somewhere within all the information produced by all the variables involved in each individual diagnosis. If we identify the full nature of cancer’s variability, we can make better choices for our patients and save more lives.”
A significant chapter within MD Anderson’s institutional research legacy will one day highlight bold steps taken to eliminate the isolation and hopelessness felt by so many patients facing uncommon cancers. Rare tumors, defined by the World Health Organization as those occurring at a frequency below six cases per 100,000 individuals per year, are challenging to treat and often are near the end of the queue for innovative therapies and research focus. While the path to progress seems arduous and obscure, MD Anderson is poised to take decisive action against the rarest and deadliest malignancies, thanks to Patient Mosaic and one person whose treatment journey catalyzed a critical aspect of the program’s vision.
William Quinton Maynard arrived at MD Anderson in search of answers but never short on hope. The rarity of his cancer, cardiac sarcoma, eluded diagnostic and treatment efforts elsewhere, and he grew exhausted of hearing a common response to his questions: “There’s little to nothing we can do.” His optimism and sheer determination, however, not only drove him to seek precise understanding of his condition, but also solidified a commitment to advancing discovery in cardiac sarcoma research so that others experiencing this disease may benefit from improved therapies. Maynard knew, thanks to the partnership he forged with his physician, Vinod Ravi, M.D., associate professor of Sarcoma Medical Oncology, that groundbreaking progress is possible and within reach — because he experienced it firsthand.
“One of the first things we did was get as much information from Quinton as we could, including genomic and immunologic data,” Ravi says. “Standard therapies were failing. At one point, the disease partially paralyzed Maynard. But he was the difference maker; his strength and internal resolve to overcome such difficult complications were remarkable. He wanted to be better, and he also was fiercely committed to discovering all we could, as quickly as we could, so other patients with rare and deadly cancers could be better, too.”
Ravi began assembling pieces. He had a wealth of information from patient history and intake. Maynard eventually moved to Houston so he could be close to MD Anderson and his care team. This helped with longitudinal observation and rapid analysis. Thanks to a robust research infrastructure, teams from the Cancer Genomics Laboratory, APOLLO, the Immunotherapy platform and several other discovery resources developed for the Moon Shots Program worked collaboratively to gather tissue samples, catalog and analyze gene functions, and interrogate this data along lines of immune profiling. With a comprehensive picture in hand, Ravi changed course from standard therapy and began treating Maynard with immune checkpoint inhibitors, which had just been introduced as a treatment option for more common cancers, including lung cancer.
“We all rejoiced when Quinton began experiencing the best outcomes to this therapy, far beyond what previous treatments produced,” Ravi says. “Through sheer will and effort, he made sure the sarcoma would not rob him of his mobility.”
While these outcomes were promising, Maynard’s cancer was advanced and aggressive. He died in 2017, yet his legacy and unyielding desire to achieve breakthroughs live on, quite literally, in the genetic information gathered throughout his journey. Maynard consented to biopsies and sample collections to develop cell-line models from tumor-acquired tissue so his care team could determine whether cell-based therapies were effective treatments against cardiac sarcoma.
“We weren’t able to answer this for Quinton, but his journey sparked a line of sight on ways to answer this for more patients with rare tumor types,” Futreal says. “What we were able to do during Quinton’s treatment in terms of outcomes and discovering the potential of creating individualized care strategies for patients with these types of rare and underdiagnosed cancers, and with limited data, these are all key reasons we want to expand and go deeper to generate more progress.”
The more we understand about the molecular features of cancer, the more pathways we may discover for novel drug development, the more personalized options we may provide patients, the more time, the more hope, all converge with an enduring vision to drive extensive discovery and save more lives. Patient Mosaic allows care teams and researchers to follow participating patients and observe every aspect of treatment. Such an all-encompassing view may lead to potential targets with therapeutic options, which then can be tested in clinical settings en route to bedsides. On a broader level, Patient Mosaic is building an unmatched dataset of patient- and tumor-derived genetic information to discover more about tumor biology and identify new potential targets for drug discovery and therapeutics development across multiple tumor types. The considerable progress and positioning accomplished so far would not be possible without vital philanthropic support.
While cancer’s many complexities present significant challenges, Patient Mosaic will help us learn how to better collaborate and digitally engage patients, who in turn are becoming active partners in their care, thanks to the amount of information we can assemble through genetic, immune and microbiomic profiling. With this in mind, the best way to ensure that patients receive optimal therapy at the most opportune time in their journey is to learn and apply as much knowledge as we can toward lifesaving breakthroughs.
This is why the program aligns perfectly with our mission to end cancer: It embraces the idea that collective knowledge gained from studying ultimately tens of thousands of participating patients and respective tumors will lead to breakthroughs that help shape the next wave of cancer treatments.
Some of the most important lifesaving cancer discoveries are rooted in seed resources provided by visionary donors who were told, or whose loved ones were told, that there was little to no hope. Indeed, stories of biomedical breakthroughs recount leaps into the unknown, interchangeable often with profiles in profound courage. They begin with a patient in need; continue with researchers committed to discovery; and culminate with clinicians resolute to provide not only hope, but specific hope envisioned at diagnosis. Such innovation requires cohesive partnership among these essential actors, and yet risk, indeterminate outcomes and the labored pace of invention are ever-present and always at odds with successful attainment.
This is where philanthropy makes a profound difference.
With ongoing support, Patient Mosaic will position MD Anderson to advance multiple technological innovations and analytical resources toward better and more effective clinical therapies. The institution prioritized this program with a $10 million investment toward an $84 million fundraising goal to complete build-out costs.
Much like the launch of the Rare Tumor Initiative, Patient Mosaic already is yielding significant results despite limited resources. This, again, is thanks to visionary early philanthropic gifts – including a significant gift from the Kotick Family Foundation -- which have enabled us to delve and measure more deeply within our population of patients with rare tumors.
Additionally, the program has begun sequencing and analyses of 212 patients’ tumor genomes and normal genomes, bridging our substantial institutional investment toward the Rare Tumor Initiative with Patient Mosaic’s operational framework, all thanks to crucial support from generous donors.
“This is going to be the largest collection of really detailed, deep, measurement-driven cancer patient data of this magnitude on the planet,” Futreal says. “Gathering all this information to help patients here today, and most importantly, help those walking through our doors tomorrow, that’s the goal. That’s how we’re going to do precision medicine.”