Caris Blog: Executive Spotlight with George W. Sledge, Jr., MD

On the heels of a great ASCO 2024, Dr. George W. Sledge, Jr., Past President of ASCO and current Caris Life Sciences EVP and Chief Medical Officer, shared his 2024 ASCO highlights, his journey in oncology and how precision medicine and the data revolution led him to Caris Life Sciences.

Active as both a laboratory and clinical researcher with more than 390 scientific publications, Dr. George Sledge has devoted his professional career as a breast medical oncologist to understanding cancer biology and improving the treatment of breast cancer. In his current role at Caris, he oversees medical affairs, research and medical education, including oversight and leadership for the Caris Precision Oncology Alliance™ and Caris’ global team of Medical Science Liaisons.

“I learned long ago that data is not knowledge and knowledge is not wisdom. Data must be mined, curated and filtered to gain knowledge.”

The 2024 ASCO slate was impressive. What themes and information stood out this year?

On the therapeutic side, this was the year of antibody-drug conjugates, in much the same way as the last decade was dominated by checkpoint inhibitors. We’re seeing an explosion in both cancers being targeted as well as new agents and increasing numbers of FDA approvals. This is important for us here at Caris because these agents typically need associated companion diagnostics, which we provide. On the diagnostic side of things, there is continuing and increasing interest in minimal residual disease (MRD) studies to identify patients at risk of relapse. This will be an important area of growth for Caris as we apply Caris Assure to MRD scenarios across the spectrum of cancer.

At Caris, we were immensely proud of our 41 collaborative studies across 19 tumor types that were accepted for presentation at ASCO. These are a testament to the value of Caris’ comprehensive molecular profiling and the power of our ever-expanding Caris Precision Oncology Alliance™ network. The diverse findings underscore the critical role of comprehensive profiling in cancer care and the power of large clinico-genomic datasets to identify new biomarkers with clinical implications. Through extensive sequencing and data analysis efforts, we’re unlocking new avenues for tailored therapies to revolutionize cancer treatment.

What can you share about your journey as a practicing oncologist?

I’ve had the honor of being a practicing oncologist for 40 years – treating patients in the clinic, researching in the lab, teaching higher learning and leading national organizations devoted to understanding cancer biology and how we can better patients’ treatment. My path to this long career in oncology was most certainly patient-driven.

As an intern, the first patient I’d ever spoken to about their terminal diagnosis was a young woman who looked up at me and said, ‘But Dr. Sledge, who will take care of my children?’ It broke my heart and was probably the most important question I’ve heard as an oncologist. Our goal as oncologists is to keep families intact and keep patients alive and well. That one question changed my life.

I’m certainly not alone within the oncology community with the heartbreak of losing a patient, especially due to the inability to find a successful treatment. It’s a devastating reality that most drugs fail most patients most of the time because cancer is smart and finds ways around therapeutics. My life’s work has been devoted to outsmarting cancer, improving the understanding and prediction of the disease and providing better care.

“My life’s work has been devoted to outsmarting cancer, improving the understanding and prediction of the disease and providing better care.”

How has precision medicine and the data revolution shaped your career?

Throughout my career, I’ve experienced many evolutions in how the oncology community diagnoses, treats and cares for patients, and I participate in the development of biomarkers for early stage breast cancer. One of the biggest challenges in the past involved matching a patient’s just-right treatment plan against their specific cancer, which often required far more information and sophisticated tools than were available. But that’s all changing. We’re living in – and treating patients through – a new era in cancer care, and Caris is at the forefront of that movement.

Over the last 5-10 years, I’ve become convinced that the future of oncology will be driven by larger and larger data sets, which will inform the interactions physicians have with patients in the clinic. The oncology field has moved from a ‘throw everything against the wall and hope something sticks’ time to a place where we now have access to data from a multitude of sources – molecular, clinical, etc. – transforming how we think of the disease and enabling new solutions to benefit patients. I’m a ‘kid in the candy store’ when I think about Caris’ unique ability to bring together enormous data sets – we have hundreds of thousands of comprehensive patient samples across the whole genome matched with clinical data. That information enables us to ask and answer many crucial questions to make an enormous difference in patient outcomes and change the face of cancer. So, I consider coming to Caris not a major change but a continuation of what I’ve been doing for decades: trying to find the right answers for cancer patients.

How is Caris unique in regard to the data revolution?

I learned long ago that data is not knowledge and knowledge is not wisdom. Data must be mined, curated and filtered to gain knowledge. Wisdom comes from combining gained knowledge with other data (i.e., claims, EHRs). That’s what sets Caris apart. As the first in the industry to provide whole exome and whole transcriptome coverage for every viable sample, Caris has amassed the largest clinico-genomic database in oncology by integrating an extensive catalog of molecular data with cancer treatment information and clinical outcomes data for more than 632,000 patients. Caris collaborates with other best-in-class companies to continue establishing the gold standard of multi-modal data versus smaller limited panels, to find correlations you wouldn’t find elsewhere and to understand how cancer changes over time in response to therapy. This is unprecedented in the field. Caris can be more effective and deliberate with our research partners in accelerating therapeutic development to help patients live longer. I believe the data revolution will lead the way in molecular diagnostics and the therapeutics will be companions going forward. In the clinic, it’s mainly going to be about data management – how oncologists decide which patients get which treatments and whether or not they will work.

How does artificial intelligence and machine learning impact cancer care?

Artificial intelligence (AI) often gets a bad rap, but in healthcare it will be transformative. Amassing enormous amounts of data is only beneficial if innovative technology is available to curate, filter and analyze it. Over the last decade, Caris has developed highly sophisticated AI bioinformatics and machine learning capabilities and trained on a massive amount of high-quality clinical and molecular data. This data and machine learning convergence has enabled Caris to identify unique, novel signatures that have demonstrated improved outcomes and increased overall survival for cancer patients. A few examples:

  • Caris FOLFIRSTai™, our AI signature molecular predictor of chemotherapy efficacy, has proven to extend survival by an average of 17.5 months for patients treated in a manner consistent with the prediction in the order in which the chemotherapies are administered.
  • Caris GPSai™ is the only diagnostic tool that looks at both DNA and RNA (over 23,000 genes in a person) to make accurate predictions on cancer tissue of origin. This helps solve for ‘Cancer of Unknown Primary (CUP),’ which is when a cancer has spread to other areas of the body, but doctors don’t know the origin, which is crucial for proper treatment.
  • By focusing on the future, Caris has developed tools and services to analyze future biomarkers – those targeted by treatments still in development. This helps oncologists match patients with treatments that are in trial or as soon as they become available. What is newly treatable today was not necessarily treatable last week. Caris’ look back program lets oncologists know if a mutation with a new FDA indication is found that can help patients, which can be lifesaving.

I often tell friends that I know where we’ll be in 10 years, but not in five. A decade from now we’ll increasingly evaluate the real-time evolution of human cancers and apply that knowledge to the successful treatment of cancer. How we get there – the 5-year timepoint – will be the exciting part of the journey. It will, like many a circus ride, be wild, adrenaline-infused and exciting to live through. But at the end of the ride we’ll be in a much better place for our patients.