The Costs of Pursuing Cancer Cures

Jori May, MD
Fellow in the Division of Hematology/Oncology at the University of Alabama at Birmingham

In this edition, Jori May, MD, reviews The First Cell: And the Human Costs of Pursuing Cancer to the Last, in which hematologist-oncologist Azra Raza, MD, asks whether medicine and our society are approaching cancer the wrong way.

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Title: The First Cell: And the Human Costs of Pursuing Cancer
Author: Azra Raza, MD
Length: 368 pages
Published: Basic Books, Hachette Book Group, New York, NY

At one of my institution’s recent journal club meetings, we discussed results from a clinical trial that eventually led to FDA approval for a new indication of a chemotherapeutic agent in a malignancy with few effective treatment options. My take-home message from the session had nothing to do with the trial itself. Instead, I felt a sadness about the almost palpable sense of resignation in the room as we acknowledged that, while the approval of yet another medication that slows disease progression by a few months is not what our patients need most, we will take what we can get.

Our group accepted the reality that we will be compelled to use this treatment, knowing that those few months of improvement observed in the trial may not be reproducible in our real-world patients, knowing that the side effects are likely to outweigh the benefit, knowing that there is financial toxicity associated with the therapy, and knowing that the disconnect between the hope for the new drug and the realities of its benefit will take a crushing emotional toll on patients. We know this but we are compelled to prescribe it anyway because it feels like the best option we have.

In The First Cell, Azra Raza, MD, brings a voice to this shared frustration and presents a data-driven, yet also very human and personal, argument for how we can and should change the way we approach cancer research to do better for our patients.

Her premise is straightforward: With a few rare exceptions, our health-care system has been generally unsuccessful in making meaningful improvements in cancer treatment; therefore, we need to rethink our approach. Dr. Raza acknowledges some successes, such as targeted therapies in chronic myeloid leukemia and acute promyelocytic leukemia and immunotherapies for certain malignancies but notes that these advances have had a proportionally small impact in terms of collective numbers and general cancer-related outcomes. By interweaving powerful statistics with personal stories of her patients, friends, and family, she encourages the reader to shift focus from the minority of patients who are treated successfully to the majority of patients who are not, bringing a voice to the anguish of failed treatment.

Dr. Raza’s proposed solution is twofold. First, she encourages the abandonment of our current methods of drug design, paying particular attention to the limitations of mouse models in consistently generating clinically meaningful therapies. Second, she calls for a shift from treating cancer once it has developed to instead identifying the first signs of cancer to prevent its development. “To begin the ending, we must end the beginning. Prevention will be the only compassionate, universally applicable cure,” she writes.

Collectively, these challenges support her desire to refocus efforts “from chasing after the last cell to identifying the footprints of the first.” She argues that once cancer is visible, it is already too late. The key to consistent cure is to find the earliest indications of cancer’s existence and eradicate these emerging clones before they have the opportunity to grow and evolve. Dr. Raza discusses multiple potential biomarkers under investigation to accomplish this goal, including microRNAs, circulating tumor DNA and clonal cells, protein signatures, and exosomes.

Her review of the current practice of drug development is scathing. She concentrates on the system’s insistent reliance on preclinical models, despite their inability to consistently predict clinical success, highlighting the multiple reasons that these models are unable to duplicate the complexity of cancer in individual patients. She identifies other factors at play, including how high economic risk of drug development encourages expanding indications rather than innovative treatment approaches, how the dearth of effective oncologic therapy allows for approval of drugs with minimal benefit, and how the rigor of clinical trials fails to reflect real-world outcomes.

Collectively, these challenges support her desire to refocus efforts “from chasing after the last cell to identifying the footprints of the first.” She argues that once cancer is visible, it is already too late. The key to consistent cure is to find the earliest indications of cancer’s existence and eradicate these emerging clones before they have the opportunity to grow and evolve. Dr. Raza discusses multiple potential biomarkers under investigation to accomplish this goal, including microRNAs, circulating tumor DNA and clonal cells, protein signatures, and exosomes.

She also touches on potential technical advances such as an implantable chip that can detect, capture, and destroy circulating cancer cells, or a “smart bra” that detects subtle tissue distortions indicative of early breast cancer development long before scheduled screening mammography. Finding the first abnormal cell is only the beginning, she writes, as the complex task of eliminating that cell is an essential final step. The feasibility of this approach is unclear, but her argument is rational, powerful, and will likely shape the future of cancer research and patient care.

I am not a laboratory scientist or translational researcher and do not participate in the processes of drug development and approval, so I cannot speak to Dr. Raza’s perspective on these arguments. I am, however, a trainee who has sat in countless journal clubs, who has found herself internalizing that sense of resignation that the current state of cancer care is the best we can do. To me, The First Cell is the story of a physician-scientist who has sat in many of those same rooms. Instead of losing hope, though, she has used the stories of her patients and her family as inspiration to demand better.