On Reinventing Cancer Care: Early Detection, Hybrid Cells & The First Cell Stage

This summary details an episode of the Live Longer World podcast, featuring a compelling conversation with Dr. Azra Raza, a distinguished hematologist-oncologist, researcher, and author of "The First Cell." The discussion, hosted by Astha Simes and featuring insights from Dr. Michael Levin, delves into Dr. Raza's provocative perspectives on the nature of cancer, its origins, the profound shortcomings of current research and treatment paradigms, and her innovative vision for early cancer detection. The episode is highly relevant for anyone touched by cancer—patients, families, healthcare professionals, and researchers—as well as those interested in the frontiers of medical technology, the ethics of healthcare, and systemic reform in medical research. Dr. Raza challenges conventional thinking and offers a potentially transformative approach to tackling one of humanity's most formidable diseases.

Key Insights

• Cancer, at its core, is a cellular rebellion where a cell seeks immortality and evades normal maturation processes. Dr. Raza posits that chronic stress and inflammation are key triggers, often leading to the fusion of a stressed tissue cell with an immune cell, creating a "cancer hybrid cell."
• The current approach to cancer research and treatment is critically flawed, heavily reliant on inadequate animal models and overwhelmingly focused on treating late-stage disease with highly toxic and expensive therapies that offer limited benefits for many. This has led to stagnant progress in survival rates for several common cancers.
• Dr. Raza's research highlights "cancer hybrid cells" (CHCs) or "polyploid giant cancer cells" (PGCCs) as pivotal in cancer's earliest stages and in disease relapse. These cells, identifiable by their large size and dual cellular markers, represent a novel target for early detection and therapy.
• A groundbreaking implantable device, the "Stentinel," is proposed by Dr. Raza and her collaborators. This device aims to continuously monitor blood for these giant cancer cells and other molecular biomarkers, offering the potential to detect cancer at its nascent "first cell stage," years before it becomes clinically apparent.
• Transforming cancer care necessitates a paradigm shift towards truly personalized medicine, emphasizing continuous wellness monitoring from birth and democratizing access to revolutionary early detection technologies, rather than reserving expensive treatments for the few.
• Systemic obstacles, including traditional academic research funding models and the profit-driven pharmaceutical industry, often stifle genuinely innovative, patient-centric approaches to cancer research and treatment.
• The human cost of cancer is immeasurable. Dr. Raza passionately advocates for a more compassionate, patient-centered approach that prioritizes not just curing the disease but healing the whole person, acknowledging the profound physical and psychological trauma inflicted by cancer and its treatments.

Defining Cancer: A Cellular Rebellion Fueled by Stress

Dr. Azra Raza offers a fundamental redefinition of cancer, moving beyond simple genetic mutations. She describes cancer as a state where a part of the body, a single cell, "decides to rebel against the entire confederacy of cells to simply be immortalized for itself." This rebellion manifests in two key characteristics common to all cancers: the cancer cell ignores growth-inhibitory signals, allowing it to proliferate endlessly, and it ceases to mature, remaining in an immature, dividing state.

When questioned about the cause, Dr. Raza points to "stress" as a primary instigator. This isn't just emotional stress but physiological stress, such as chronic inflammation or persistent infections (e.g., Hepatitis B in the liver). Under such duress, cells are in a "fight or flight" situation. One survival strategy they can employ is fusion. While fusion between similar cells (e.g., two liver cells) can be a normal stress response to bolster defenses, Dr. Raza highlights the critical danger of "heterotypic fusion"—when a stressed tissue cell fuses with a different cell type, often a blood cell (like an immune cell) that has arrived at the site of inflammation. This fusion creates a "cancer hybrid cell" (CHC) or, due to its often massive size and multiple nuclei, a "polyploid giant cancer cell" (PGCC). These hybrid cells express markers from both parent cell types, making them unique.

Dr. Raza's research, including filtering the blood of her pre-leukemia and leukemia patients, led to the discovery of these giant cells, sometimes 100-300 microns in size compared to a normal 15-micron blood cell. Subsequent investigations, including analysis of single-cell RNA-seq data from various solid tumors (colon, breast, thyroid, liver, etc.), have confirmed the presence of these CHCs in "every single liquid or solid cancer that has been examined." While rare, they are consistently found. Importantly, while such hybrid cells can occasionally be found in normal tissue surrounding a tumor or even in healthy individuals (often linked to temporary infections), their gene expression profiles are vastly different. Hybrid cells in malignant areas exhibit high telomerase expression (linked to immortality) and a strong inflammatory transcriptomic profile, which are absent in those found in normal settings.

The "Stentinel": A Vision for Continuous Early Detection

Frustrated by the current paradigm of detecting cancer only when it's often too late, Dr. Raza and her collaborators at Columbia University, biomedical engineers Sam Sia and Ken Shepard, are developing a revolutionary device called the "Stentinel." The name itself is a portmanteau of "stent" and "sentinel." This implantable device, resembling a tiny coronary stent, is designed to be placed in a large blood vessel in the arm and remain there, potentially from birth to death.

The Stentinel employs electrochemical impedance spectroscopy. It generates a minute electrical current; as blood cells pass through this field, they cause a disturbance (impedance). The key is that larger cells, like the PGCCs, will create a significantly larger impedance signal than normal blood cells. This allows for the continuous, real-time detection of these suspected "first cancer cells." The device is equipped with a chip to record these events and transmit the data to the cloud for AI-powered analysis. Alerts could then be sent to the individual's smartphone, indicating that "some trouble is brewing." Dr. Raza mentioned that this device could scrutinize the entire five-liter blood volume of an adult approximately every 18 days.

Beyond cell size, the Stentinel is also being developed to detect molecular biomarkers—minute pieces of protein, RNA, or DNA—associated with the early inflammatory "stage-setting" for cancer. Dr. Raza envisions a future where the Stentinel could even be programmed to "electrocute" a detected giant cancer cell, nipping cancer in the bud. She emphasizes that this technology is not just a faster horse but an "automobile" or even a "jet plane" in the era of horse carriages, representing a leap in diagnostic capability. The aim is to democratize early detection, making it accessible and affordable, extending beyond cancer to other chronic diseases by identifying the transition from wellness to illness.

A Scathing Critique of Modern Cancer Research and Treatment

Dr. Raza pulls no punches when assessing the current state of cancer research and treatment, labeling much of it a failure despite decades of effort and vast expenditure. A central theme of her critique is the over-reliance on flawed preclinical models, particularly animal models. She recounted her early career realization that drugs effective in childhood leukemia were ineffective in adults with the same disease, highlighting that the "soil" (the rest of the body's cells) is as important as the "seed" (the cancer cell). "How are we using animal models to try and develop drugs," she questioned, "when that animal does not get that cancer spontaneously?" She quoted Norbert Wiener: "The best model for a cat is another cat, preferably the same one," underscoring the need to study human cancer in humans.

This reliance on poor models contributes to staggering failure rates in drug development. Dr. Raza cited that 86.7% of Phase 1 cancer clinical trials (costing $60 billion in one year in the US) "completely bombed" because preclinical data from artificial models didn't translate to humans. Even the 5% of drugs that succeed are often not curative for advanced cancers, merely extending survival for a fraction of patients. She pointed to CAR-T therapies as an example: while hailed as breakthroughs, they've reached only 27,000 patients in 10 years (out of nearly 20 million cancer cases), cost around a million dollars per patient, cause severe toxicities (as they can't distinguish between normal and malignant B-cells), and yield a median survival of only 14 months for many recipients. For common advanced cancers like glioblastoma or pancreatic cancer, she stated that outcomes are "no different today... than it was a hundred years ago." Even in her specialty, Acute Myeloid Leukemia (AML), the standard "7 and 3" chemotherapy regimen from 1977 remains the mainstay, with 5-year survival only inching from 26% to 28%, largely due to better supportive care, not better drugs.

Dr. Raza attributes this stagnation to several systemic issues: doctors are trained to treat, not prevent; a chasm exists between clinicians seeing patients and researchers in labs; government funding agencies often dictate research directions, favoring conventional approaches and animal models; and the pharmaceutical industry is, by design, profit-motivated. Her own efforts to fund her extensive human tissue repository and the Stentinel project have faced immense hurdles, with investors even asking for studies on "doctors' behaviors" before committing funds—a level of scrutiny she feels is not applied to conventional drug development.

The "First Cell Stage" of Cancer: A New Window for Intervention

Dr. Raza's work champions the concept of the "first cell stage" of cancer. This is not Stage 1 cancer as conventionally understood, but a much earlier phase, potentially years before clinical detection. It's characterized by the presence of biomarkers indicative of chronic inflammation (the "stage being set") and the appearance of the first cancer hybrid cells (CHCs/PGCCs). Detecting cancer at this nascent stage, she argues, opens up possibilities for reversal through relatively simple interventions, such as lifestyle changes or existing drugs like metformin or Ozempic, primarily by addressing the underlying inflammation.

To identify the signatures of this "first cell stage," Dr. Raza has meticulously built a tissue repository since 1984, containing over 60,000 longitudinally collected samples (blood, serum, plasma, saliva, bone marrow aspirates, and uniquely, cryopreserved bone marrow biopsies that maintain tissue architecture) from thousands of her patients. This invaluable resource allows for multi-omics studies to pinpoint the molecular changes preceding and accompanying the emergence of the first cancer cells. She is also studying high-risk populations, such as cancer survivors, who have a 13% higher individual risk of developing a new, secondary cancer (and account for 20% of all new cancers in the US), to catch these early events. The Stentinel, she believes, is the key to translating these research findings into a practical, personalized early detection strategy. While the device itself may be universal, the interpretation of its data and subsequent interventions must be tailored to the individual.

The Human Imperative: Compassion and Patient-Centered Healing

Underpinning all of Dr. Raza's scientific pursuits is a deep-seated compassion, born from decades of frontline patient care and personal loss—her husband died of cancer, an experience that profoundly shaped her and her daughter. She speaks eloquently about the "psychic violations" inflicted upon patients and families, criticizing the medical establishment for often celebrating "game-changing therapies" that are mere technologies offering marginal benefits at great human and financial cost. "Cancer is a silent killer," she notes, often reaching Stage 4 before detection, and "no age is immune."

When a patient receives a cancer diagnosis, Dr. Raza stresses that the "only good news" is if it's caught early. For those diagnosed, she advises them to first understand if their disease is curable and what the treatment strategies entail. Given the overwhelming nature of the diagnosis, which can move a person into what she calls the "kingdom of the dead," she emphasizes the importance of seeking information and, crucially, finding a doctor who communicates well, is sympathetic, and is concerned with "healing" the whole person, not just "curing" the disease. She quotes Emily Dickinson: "Surgeons must be very careful when they test their knife / For underneath their fine incisions rests the culprit life," to illustrate that medical intervention must consider the complex human being, not just the tumor. This holistic, compassionate approach is, for Dr. Raza, as vital as any technological advancement.

Conclusion: A Call for a Revolution in Cancer Care

Dr. Azra Raza's appearance on the Live Longer World podcast offers a powerful and urgent call for a fundamental revolution in our approach to cancer. She compellingly argues that the current paradigm, fixated on treating late-stage disease with often inadequate and brutal methods, is failing too many. Her vision, centered on understanding and detecting cancer at its "first cell stage" through innovative technologies like the Stentinel, promises a shift towards proactive, personalized, and continuous health monitoring. By challenging entrenched dogmas in research and advocating for a system that prioritizes patient well-being and early, accessible detection over incremental, high-cost treatments, Dr. Raza's work embodies a profound hope. It's a hope not just for significantly better cancer outcomes, but for a more humane, compassionate, and ultimately more effective system of medicine that truly values each individual life from its earliest moments of vulnerability.