The era of genomic oncology is defined by complexity. Over the last decades, we have moved from single-gene tests to multi-gene panels and, eventually, will be routinely using whole-exome/whole-genome and transcriptome sequencing in clinical care.
For clinicians, interpreting these data and determining actionable targets has become more daunting. For patients, understanding the implications of somatic and germline findings can be overwhelming.
Our prior research revealed that nearly 25% of oncologists lacked confidence in using genomic data, underscoring the need for education and infrastructure. To address this problem at City of Hope, we launched molecular tumor boards and just-in-time peer-to-peer “consults” across our system to support test interpretation and guide clinical decisions.
Contrary to early assumptions, patients overwhelmingly want genomic information, even when it doesn’t directly affect their own treatment. In our very early NIH-funded whole-exome pilot implementation studies, more than 95% of cancer patients with advanced disease opted to receive all actionable results, including germline information, citing potential benefits for themselves and family members.
Psychological assessments consistently show low levels of distress, reinforcing that transparency and support, not withholding information, are key.
Scaling precision medicine at City of Hope
For decades, germline testing was reserved for patients meeting stringent criteria: family history, early onset or specific tumor types. These rules made sense when tests cost $4,000 to $5,000 and turnaround times were long. Today, with costs under $250 and results available in days, these barriers are outdated and inequitable.
Our prior research revealed that nearly 25% of oncologists lacked confidence in using genomic data, underscoring the need for education and infrastructure.
Our INSPIRE study at City of Hope, led by Dr. Stephen Gruber and myself, tested nearly 7,000 patients for both tumor and germline mutations and more than 20,000 patients for germline testing alone. The findings were striking: Nearly half of individuals with inherited cancer risk would have been missed under current guidelines.
This evidence demands a paradigm shift toward universal or near-universal testing for patients with cancer.
Traditional models require pre-test counseling, which creates bottlenecks and delays. City of Hope has demonstrated that eliminating mandatory pre-test counseling while ensuring robust post-test support dramatically improves access without compromising patient understanding or psychological well-being. In fact 98% of patients in our program opted for testing, and distress levels remained low.
Looking ahead: Early detection and AI integration
Beyond genomics, City of Hope is exploring multi-cancer early detection strategies, including whole-body MRI combined with liquid biopsy. In a pilot study of high-risk individuals that I conducted with Dr. Dan Raz, we identified asymptomatic cancers and precancerous lesions, while reducing cancer-related anxiety in 85% of participants.
As we anticipate the next decade, artificial intelligence and large language models will transform oncology— from clinical trial matching to deriving multi-omic insights from pathology slides.
At City of Hope, our mission is clear: Deploy these innovations thoughtfully and equitably, ensuring every patient benefits from the future of precision medicine.
City of Hope® is one of the largest and most advanced cancer research and treatment organizations in the U.S. To learn more about City of Hope, visit: www.cityofhope.org.
Discover the latest innovations in cancer research on City of Hope’s new podcast, “On the Edge of Breakthrough: Voices of Cancer Research.” Available on Spotify, Apple Podcasts and at cityofhope.org/edge-of-breakthrough.
