Precision Cancer Medicine
What is Precision Cancer Medicine?
Therapies for cancer have traditionally been based on the tumor site, like breast cancer or lung cancer. More recently, researchers have found that cancers across tumor sites have common genetic mutations – changes within the DNA of a cell – and those mutations can be targeted with specific drugs.
The future of cancer medicine goes beyond looking at cancer by tumor site, using genetic sequencing to uncover a patient’s specific tumor mutations and deliver personalized therapies. While the field of precision cancer medicine has advanced in recent years, we are still discovering new cancer-causing genetic mutations and developing personalized therapies that can treat them.
A 360-Degree Approach to Precision Cancer Medicine
Here at HICCC, we’re attacking cancer from all sides — using cutting-edge technologies and innovative approaches like:
- Genetic sequencing
- Computational models that help physicians understand each patient’s unique cancer
- Access to the latest treatments such as immunotherapy
- World-class multidisciplinary teams that deliver the top care to our patients
We look at solving cancer differently, learning from different disciplines and applying the newest approaches to research. We aren’t focused on just curing cancer—we aim to end it entirely, stopping it in its tracks before it even begins.
We use cutting-edge genetic sequencing, computational models that help physicians understand each patient’s unique cancer, access to the latest treatments such as immunotherapy, and world-class multidisciplinary teams that deliver the top care to our patients.
The Power of Predictive Mathematics
Researchers at the HICCC have turned cancer research on its head. Rather than targeting each possible pattern of genetic mutations that drives cancer, they’re honing in on the network of proteins that are crucial for keeping cancer alive. Mathematicians and computational biologists in Columbia’s Department of Systems Biology have developed algorithms to predict and prioritize drugs and drug combinations, based on these complex models of cell networks, that will most effectively kill cancer cells.
What Comes Next: N-of-1 Trials
Using this network approach, we’ve launched a new kind of RNA-based clinical trials, called “N-of-1 trials.” Conducted in one patient at a time, N-of-1 clinical trials explore different treatment options based on each patient’s unique genetic makeup and cancer biology. Using methods developed in our labs, our N-of-1 clinical trials aim to identify the specific genetic and molecular factors that are key to each patient’s cancer, and to find the right therapies to stop the cancer.
Going Beyond Next-Generation Sequencing
Next-generation sequencing has provided the foundation for precision medicine. These new tests allow researchers and physicians to look at the building blocks of DNA and identify mutations of many genes at once. Columbia’s Center for Precision Cancer Medicine goes beyond next-generation sequencing to use the most advanced genetic testing, innovative RNA-based biomarkers and diagnostic tests developed here at Columbia.
Where DNA is the book that stores information about each person’s genetic expression, RNA is the reader that decodes it. RNA is more complex and can provide a deeper view into a patient’s genome, allowing researchers and physicians to identify more precise targeted treatments for each patient.
From the Bench to the Bedside, and Back Again
Taking all of the personalized data for each patient, a team of precision cancer medicine clinical experts work together to identify the best treatment options. Oncologists, pathologists, surgeons, radiologists, immunologists, genetic counselors and others come together at weekly molecular tumor boards to review each patient’s case and the newest potential treatments.
Using samples from a patient’s tumor, researchers can develop personalized tumor models to test multiple therapies. This gives researchers important insights for developing more effective future therapies and diagnostic tools.
Precision Cancer Tests and Sequencing at the HICCC
Precision cancer medicine is a rapidly advancing field, and here at the HICCC, we are proud to be at the forefront with the wide array of genetic tests and sequencing we offer, many of which were developed in our own laboratories. Your clinical care team at the HICCC will discuss with you any genetic tests that they might recommend.
Center for Precision Cancer Medicine
HICCC and Columbia are expanding their role as leaders in this growing field with the newly established Center for Precision Cancer Medicine. Led by Adam Bass, MD, the center will develop an robust program of physician-scientists dedicated to expanding our understanding of the relationship between cancer genetics and treatment. One key initiative within the center will focus on sequencing patients’ tumors during treatment with the goal of developing new targeted therapies. The center will collaborate with Columbia’s Department of Systems Biology to interpret this incredibly complex data.
For Clinicians and Researchers
Below are some of the genetic testing offered at the HICCC to identify actionable genetic markers for therapies. For more information about additional testing, visit the Columbia Pathology website.
Precision Cancer Tests and Sequencing
Columbia Combined Cancer Panel (CCCP)
The Columbia Combined Cancer Panel (CCCP) is a 467-gene cancer panel designed by NewYork-Presbyterian/Columbia physicians and pathologists and currently only offered at NewYork-Presbyterian/Columbia. It is approved by the NYS Clinical Laboratory Evaluation Program (CLEP) for clinical use.
Columbia Targeted Fusion Panel (CTFP)
The Columbia Targeted Fusion Panel (CTFP) is designed to understand gene fusions that are often detected in solid tumors including lung tumors, thyroid tumors, gliomas, and others. The CTFP uses Anchored Multiplex PCR (AMP) chemistry (Archer Dx, CO) followed by next-generation-sequencing (NGS). AMP utilizes unidirectional gene-specific primers (GSPs) that enrich for both known and novel fusion partners in key genes. Gene fusions can aid in classification of specific disease entities, and provide information for risk stratification. Chimeric proteins encoded by the gene fusions can serve as specific therapeutic targets, resulting in improved patient outcomes.
DarwinOncoTarget™ and DarwinOncoTreat™
The DarwinOncoTarget™ and DarwinOncoTreat™ tests analyze whole transcriptome sequencing (RNASeq) of a patient-derived tumor sample to identify aberrantly activated proteins for which a clinically relevant targeted inhibitor already exists and to match tumor-specific dependencies with clinically-relevant drugs, respectively. By clinically relevant we mean FDA approved drugs as well as investigational drugs in Phase 2 and 3 clinical trials. More specifically, the DarwinOncoTarget™ test currently assesses aberrant activity of 193 proteins that can be targeted by 94 FDA approved oncology drugs, and by 239 investigational oncology agents. These numbers will change as more information becomes available. The DarwinOncoTreat™ test first identifies tumor-checkpoints comprising master regulator proteins that represent critical tumor dependencies; this is accomplished by assessing the concerted activity of 6,293 regulatory proteins. It then prioritizes drugs based on their experimentally tested ability to revert the activity of the tumor checkpoint in appropriate cell line models. While DarwinOncoTarget™ is available for all human malignancies, DarwinOncoTreat™ is currently available only for specific tumor subtypes for which the experimental assessment has already been completed (currently, breast carcinoma, glioblastoma multiforme, meningioma, neuroendocrine tumors, and sarcomas). Additional tumor subtypes will be added as the experimental validation data becomes available.
For patients with advanced cancers who have failed standard therapy these results may help the oncologist prioritize potential drug targets or select clinical trials.
Cancer Whole Exome Sequencing (cWES) is a type of genetic testing that analyzes tumor DNA to determine if any mutations exist that can cause disease. cWES searches through the protein-coding portions of a genome (the “exome”) and is one of the most comprehensive types of genetic sequencing offered for advanced cancer profiling. Most errors in a DNA sequence that lead to altered protein function in tumors are located in the exons, making exome sequencing an efficient method of analyzing genetic causes for tumor genesis and behavior. cWES is designed to detect actionable constitutional changes predisposing to cancer as well as cancer-specific single nucleotide variants (SNVs), indels and structural variations.
Molecular Tumor Board
Adult and pediatric cases genetically sequenced through the Laboratory of Personalized Genomic Medicine at Columbia University Irving Medical Center are presented at a weekly molecular tumor board. The molecular tumor board brings together a diverse, multi-disciplinary group of medical oncologists; molecular and surgical pathologists; genetic counselors; as well as medical students, residents and fellows.
The discussions include clinical best practices, clinical recommendations based on specific mutational profiles, clinical trial matching, and referrals to medical genetics. This interdisciplinary meeting provides a platform that integrates clinical and molecular parameters to find the best therapies for each patient.
A survey of molecular tumor board attendees was conducted in 2019 to obtain feedback regarding the indications for attendance and utility of information provided during the meetings. The results were uniformly positive:
- 89% of participants agreed that the discussions provided critical targeted therapy recommendations
- 95% reported they had received information regarding appropriate genetics evaluation of secondary findings
- 88% agreed that the information provided during the tumor board could be used to guide referrals for additional specialist evaluation, and
- 94% felt that sequencing results presented during tumor board discussions provided diagnostic or prognostic information