MSK researchers publish new review that focuses on genome-driven oncology

Feb 9 2017

Researchers from Memorial Sloan Kettering Cancer Center (MSK) today published a seminal review of the rapidly evolving field of precision oncology, which allows doctors to recommend therapies based on a genetic understanding of a person's cancer. Appearing in the special cancer-focused February 9 issue of Cell, the article — "Implementing Genome-Driven Oncology" — presents a critically self-reflective but solutions-focused perspective on this approach to cancer treatment.

"This is a transformative time for cancer therapy," explained José Baselga, MD, PhD, Physician-in-Chief and Chief Medical Officer at MSK and the review's senior author. "By taking a moment of pause to look back on what we have achieved, we can we move forward and identify how best to tap into the full potential of genome-driven oncology. This review provides a proposed framework to begin addressing critical knowledge and implementation gaps and ultimately to providing better outcomes for patients worldwide."

The article reviews the underlying science and early clinical successes of precision oncology, including:

•Tailor-Made Patient Care: Precision oncology has dramatically extended some patients' lives. More than 30 promising gene targets were identified in the formative years of this field and, as a result, nearly 25 targeted therapies have been approved by the FDA. In addition, research is yielding important information about acquired resistance and how to prevent it.

•An Unprecedented Design for Clinical Trials: Basket trials — in which patients enroll in a clinical trial to receive a therapy based on the mutation driving their cancer, rather than where the tumor initially appeared in the body — have allowed patients to more easily access the newest drugs while helping researchers quickly obtain crucial data that can lead to FDA approval and more widespread use of a new therapy.

•Technological Advances: The promise of precision oncology hinges on the continual improvement of technology, from sequencing to data sharing. These advances will pave the way for precision research tools such as liquid biopsy and RNA sequencing to become mainstream.

In addition to these successes, the MSK authors address criticisms of the value of precision oncology, including the debate around how many patients this approach can benefit; the fact that many patients lack access to large cancer centers that offer tumor sequencing; the inevitable challenge of acquired resistance; and obstacles surrounding clinical trials, such as limited access, low enrollment, and a lack of consensus over the best design.

The review also provides guidance on how best to forge ahead into a new era of precision oncology with the collective goal of increasing our insights into cancer and providing better treatment options for patients worldwide. The authors urge a focus on overcoming roadblocks in data sharing across institutions, robust efforts to hone clinical trial design and increase enrollment through the democratization of access in the community, and improving sequencing technology to continue the identification of actionable mutations.

The Current Landscape
The recent explosion of interest in genome-driven oncology was amplified by the National Cancer Moonshot Initiative, launched in 2016 and led by former Vice President Joseph Biden. Leading cancer centers around the world are reporting improvements in sequencing technologies, with the goal of discovering more actionable mutations and a wealth of data that can be broadly shared. These efforts have significantly improved access to genomically matched clinical trials in the community, where the majority of cancer patients are treated.

"Clinical trials have evolved from studies that treated cancers based on single tumor types to those based around genetic alterations," said David Hyman, MD, Director of Developmental Therapeutics at MSK and another coauthor. "Targeting validated biomarkers in different cancer types is an opportunity to immediately extend the benefits of precision oncology. Not even two years ago, we published the findings from the first 'basket trial,' a type of research study that concentrates on a specific mutation found in the tumor, regardless of where the cancer originated. Since then, basket trial design has become an increasingly important approach to treatment and has already begun to change clinical practice, providing new treatment options for patients."

Navigating the Challenges
Stressed throughout the review is the fact that precision oncology is not a one-size-fits-all approach to cancer treatment. Obstacles to broad implementation include challenges credentialing and validating drug targets, implementing drug combinations, designing clinical trials, addressing tumor heterogeneity, and deploying techniques beyond DNA sequencing. The authors note that these challenges are not indictments of the therapeutic approach and that many of the criticisms are part of a learning process. In the face of such critiques, the authors call for a greater commitment to precision studies and confidence in the field based on underlying science and early clinical successes.

"We are at the end of the beginning of this process. We have learned a lot and we have a lot to learn," explained Barry Taylor, PhD, Associate Director of the Marie Josée and Henry R. Kravis Center for Molecular Oncology (CMO) at MSK and a third coauthor of the study. "Precision oncology is an attractive yet challenging strategy. A healthy dose of skepticism is essential to advancing a scientific dialogue."

A Future for Precision Oncology
While calling for greater collaboration, the authors note that progress cannot be achieved through today's conventional approaches. The complexity of human cancers is simply greater than can be reflected by the data any single center or commercial lab can generate. Sharing knowledge and democratizing access to this information is key to bringing the benefits of precision oncology to more patients.

With all the new and powerful tools available, the authors cite an "engineering" issue as the main roadblock to broad implementation of genome-based cancer care. Improving efficacy from start to finish needs to be a real focus, and maximizing progress will require multidisciplinary teams to improve every step in the precision oncology ecosystem. If done correctly, the research community will finally have the tools to make truly transformative insights into the basic biology of cancer and its treatment.

Genome-Driven Oncology at MSK
As evidenced by the establishment of the CMO and the creation of a powerful genomic sequencing test called MSK-IMPACT, MSK leadership saw the promise of precision oncology early on and committed to realizing its ability to create better treatment options for all people with cancer. With more than 800 clinical trials currently open, MSK has a strong clinical-trial infrastructure. After launching a comprehensive survey and determining that only 4 percent of all patients enroll in clinical trials for cancer each year nationwide, the MSK community is actively working to expand participation.

In addition to having a leading role in data-sharing initiatives such as AACR Project GENIE, MSK has created number of its own initiatives aimed at increasing DNA sequencing in minority populations and patients around the world. The institution launched the MSK Cancer Alliance in 2014 aimed at improving quality of care and outcomes for people with cancer in community settings. These are just a few examples of the work being done to break down silos, increase collaboration and information exchange, and ultimately expand access to new precision treatments. MSK's exceptionally powerful and seamless integration of clinical and scientific teams makes it uniquely situated to help design the future of precision oncology.