April is Esophageal Cancer Awareness Month — a time to spotlight a disease that remains understudied, yet deeply in need of better tools for detection, monitoring, and treatment. Valsamo (Elsa) Anagnostou, MD, PhD, Professor of Oncology at Johns Hopkins School of Medicine and a Torrey Coast Foundation GEMINI CRI CLIP Investigator, is working to understand how cancers evolve during treatment – and how emerging technologies like liquid biopsies could help physicians stay one step ahead.
Understanding Cancer as a Moving Target
Cancer is not static. Tumors constantly change — especially under the pressure of treatments like immunotherapy. This process, known as cancer evolution, is a major challenge in oncology. Even when therapies initially work, cancer cells can adapt, survive, and eventually return.
Dr. Anagnostou’s lab studies this phenomenon by combining experimental biology with computational data science, analyzing both tumor tissue and fragments of tumor DNA circulating in the blood.
Dr. Anagnostou’s work is centered on capturing how cancer evolves during therapy, either by analyzing tumor tissue or by detecting tumor DNA in the bloodstream using liquid biopsy approaches. That mission is especially urgent in gastroesophageal cancers, where scientific discoveries have not always translated into improved outcomes for patients.
The Challenge of Recurrence
For patients diagnosed with esophageal cancer – even at an early stage – the risk of recurrence remains high. Many patients undergo surgery and chemotherapy with curative intent; however, for those with stage 2 or 3 disease, the cancer often returns within just a couple of years.
This raises two critical questions:
- How can we prevent recurrence after initial treatment?
- How can we better tailor therapies to each patient?
Esophageal cancer is not a single disease but a biologically diverse one. That heterogeneity makes it harder to predict which patients will benefit from specific treatments — and who may need a different approach.
A Blood Test That Could Change Everything
One of the most promising tools in this space is the liquid biopsy. Unlike traditional biopsies, which require tissue samples, liquid biopsies analyze tumor-derived DNA circulating in the bloodstream, known as circulating tumor DNA (ctDNA). These fragments are released when cancer cells die, offering a minimally invasive window into the tumor’s biology. Dr. Anagnostou believes that this approach has the potential to fundamentally change how cancer is monitored.
Liquid biopsies provide a sensitive and rapid way to detect cancer and create new opportunities for real-time monitoring, which would ultimately transform the way we personalize cancer treatment.
In a recent clinical study, her team found that patients whose ctDNA cleared before surgery had significantly better outcomes. In contrast, those with residual ctDNA – evidence of lingering disease – faced a higher risk of recurrence. Even more striking, ctDNA revealed important differences among patients who otherwise appeared similar based on standard pathology. This kind of molecular insight could help clinicians better predict outcomes and refine treatment strategies.
Immunotherapy: A Turning Point
The treatment landscape for esophageal cancer is also evolving, thanks in part to immunotherapy. In early-stage and locally advanced disease, perioperative immunotherapy given before and after surgery is beginning to change outcomes. While not every patient responds to immunotherapy, these advances mark an important shift in the care paradigm — and underscore the need to better understand why some tumors respond while others do not.
A central challenge in cancer research is understanding resistance to therapy. Some tumors respond initially, but later recur, while others never respond. Resistance is complex, driven by multiple factors, including genetic mutations within cancer cells, changes in the tumor microenvironment, and broader biological shifts that allow tumors to evade the immune system.
To truly understand response and resistance, we need a holistic view — one that integrates genetic, molecular, and cellular data to uncover what’s driving each patient’s disease.
These “multi-omic” approaches are helping researchers identify biomarkers that can guide treatment decisions and reveal new therapeutic opportunities.
Toward Truly Personalized Cancer Care
Looking ahead, the future of esophageal cancer treatment may be defined by adaptability.
Instead of relying on a one-time snapshot of a tumor, clinicians could continuously monitor how a cancer responds and adjust treatment accordingly.
In this model:
A patient’s tumor is matched with therapy based on its biology
Liquid biopsies track treatment response in real time
Treatment is refined based on molecular feedback
Dr. Anagnostou envisions this as a powerful combination: pairing an understanding of tumor biology with real-time monitoring to optimize care.
The integration of immunotherapy into earlier stages of treatment, combined with advances in liquid biopsy technologies and deeper biological insights, is opening new possibilities for patients. For Dr. Anagnostou, this convergence is what drives optimism. She points to progress on multiple fronts – from more effective therapies to better tools for measuring response – as reasons for hope.
I’m very encouraged by the advances in immunotherapy for early-stage gastroesophageal cancer. As we deepen our understanding of how tumors respond and resist treatment, and continue advancing liquid biopsy technologies, I’m hopeful we can better optimize care and improve outcomes for patients
