Why did Dr. Azra Raza choose oncology as her specialty?

Dr. Raza's interest in oncology stemmed from her childhood fascination with science and a desire to reduce human suffering. Witnessing hugely advanced, end-stage cancers in Karachi, Pakistan, as a medical student, coupled with the intellectual challenge of understanding cancer's origins, solidified her commitment to the field. Oncology was also one of the few avenues into scientific research available in Pakistan at the time.

How has the age-adjusted cancer mortality rate changed over the past century?

According to Dr. Raza, the age-adjusted mortality rate for cancer in 2020 is the same as it was in 1930. The perceived decline in mortality over the last 30 years largely parallels the decline in smoking rates, rather than significant breakthroughs in treatment for advanced cancers.

What is the primary treatment approach for most cancers, and how effective is it?

The primary treatments for 68% of newly diagnosed cancers today remain 'slash, poison, and burn'—meaning surgery, chemotherapy, and radiation. While effective for early-stage or certain responsive cancers (like Hodgkin's lymphoma), these methods are largely ineffective for the 32% of patients who present with advanced, metastatic disease.

What are the limitations of modern targeted therapies and immunotherapies like CAR T-cells or checkpoint inhibitors?

While therapies like Gleevec for CML and ATRA for APL have been successful for specific rare cancers, and checkpoint inhibitors show promise, their overall impact on cancer mortality is less than 10%. Dr. Raza criticizes CAR T-cells for their inability to distinguish between normal and cancer cells, leading to indiscriminate organ destruction and severe side effects. Similarly, checkpoint inhibitors, despite positive responses, can cause devastating autoimmunity.

How do pharmaceutical companies and regulatory bodies contribute to the high cost and limited efficacy of cancer drugs?

Dr. Raza argues that incentives are misaligned, leading pharmaceutical companies to prioritize profit over patient benefit. Drugs like a modified '7 and 3' chemotherapy combination, costing $45,000 for a marginal survival improvement of 3.7 months, illustrate this. Regulatory bodies like the FDA are critiqued for lowering approval standards under pressure from advocacy groups, leading to the approval of drugs with minimal clinical benefit at exorbitant prices, financially ruining patients.

What are the fundamental flaws in current cancer research models, such as cell lines and animal studies?

Current research models rely heavily on cell lines and animal models (like mice), which Dr. Raza views as overly artificial. Immortalized cell lines often undergo 'transcriptomic drift' and no longer faithfully represent human cancers, making drug testing irrelevant. Animal models, particularly for drug development, frequently fail to extrapolate to humans, contributing to a 95% failure rate of experimental agents and irreproducible research findings, wasting vast resources.

What is Dr. Azra Raza's proposed solution to the 'war on cancer' and why is she optimistic about the future?

Dr. Raza advocates for a dramatic shift in resources, proposing 50% of funding should go towards prevention and early detection, rather than the current 5%. She believes cutting-edge technologies like genomics, metabolomics, advanced imaging, and microfluidics-based chips (like the m-chip and liquid biopsies) can identify the earliest footprints of cancer. She is optimistic because the technology exists to monitor the human body continuously for biomarkers, which, if studied in human samples rather than artificial models, can lead to revolutionary early detection strategies.

How did Dr. Raza cope with the loss of her husband, Harvey Preisler, to leukemia?

Dr. Raza experienced profound grief, anger, and crying fits during her husband's five-year battle with leukemia. She describes kicking doors and questioning the unfairness of the situation. Her husband, Harvey, was the one who reached a point of acceptance, calmly reassuring her not to worry. She eventually found strength in his acceptance and in the 'toil of love' of caring for him and their young daughter.

What is the significance of Dr. Raza's tissue repository?

Since 1984, Dr. Raza has meticulously collected over 60,000 samples (blood, bone marrow, T-cells, buccal smears) from thousands of patients, serially followed for years. This national treasure of human tissue samples, collected with her own hands from the 'first cell' to advanced disease, holds the key to tracing disease origins, identifying early biomarkers, and understanding the natural history of cancer, providing a robust foundation for future research.

Key Moments

#121 – Azra Raza, M.D.: Why we’re losing the war on cancer

Peter Attia MD

People & Blogs3 min read115 min video

Jul 28, 2020|5,506 views|170|36

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Key Moments

TL;DR

Cancer research progress is limited; focus needs to shift to early detection and prevention.

Key Insights

Current cancer research models and return on investment are inefficient, leading to a lack of significant progress in survival rates.

The "slash, poison, burn" approach (surgery, chemotherapy, radiation) has seen minimal improvement in treating advanced cancers over 90 years.

Targeted therapies and immunotherapies, while promising, have had limited impact on overall cancer mortality, often benefiting rare subtypes or offering only marginal survival gains.

The high cost of cancer drugs and treatments is financially ruinous for patients, driven by a system prioritizing profit over patient well-being.

Current research platforms, like cell lines and animal models, are often artificial and non-reproducible, hindering meaningful drug development.

A paradigm shift towards early detection, utilizing advanced technologies like genomics, proteomics, and liquid biopsies, is crucial for improving outcomes.

Prevention through lifestyle changes, though important, doesn't explain cancer incidence in the majority of cases, highlighting the need for better early detection methods.

THE INADEQUACY OF CURRENT CANCER RESEARCH MODELS

Dr. Azra Raza argues that the current model of cancer research, despite massive investment, yields a poor return on investment and has failed to significantly improve survival rates. She highlights that the fundamental treatments remain "slash, poison, burn" (surgery, chemotherapy, radiation), with minimal advancements for advanced-stage cancers over decades. This critical assessment is driven by her personal and professional experiences, emphasizing the urgent need for a paradigm shift.

THE illusion OF PROGRESS: TARGETED THERAPY AND IMMUNOTHERAPY

While targeted therapies like Gleevec and immunotherapies like checkpoint inhibitors have shown success, Raza contends they primarily benefit rare cancer subtypes or offer only modest survival extensions for a fraction of patients. These advances, though celebrated, have not translated into substantial overall reductions in cancer mortality, and complex treatments like CAR T-cell therapy can have severe, indiscriminate side effects, often not distinguishing between cancerous and healthy cells.

FINANCIAL TOLL AND ETHICAL CONCERNS IN CANCER CARE

The exorbitant cost of cancer drugs and treatments is financially devastating for patients, often leading to bankruptcy and relentless collection efforts. Raza criticizes the system where pharmaceutical companies and even non-profit hospitals prioritize profit, leading to artificially inflated drug prices and a focus on incremental survival benefits rather than cures. The pressure to gain FDA approval often lowers standards, approving drugs with minimal impact at astronomical costs.

THE FLAWED PIPELINE OF DRUG DEVELOPMENT

A significant issue highlighted is the unreliability of current preclinical research models, such as cell lines and animal models. These models are often artificial, genetically skewed, and irreproducible, leading to a 95% failure rate for experimental cancer drugs. This flawed pipeline means that billions of dollars are spent on research that rarely translates into effective human treatments, perpetuating a cycle of futility.

THE IMPERATIVE OF EARLY DETECTION AND PREVENTION

Raza strongly advocates for a fundamental shift in focus towards early detection and prevention. She argues that the only strategy that has consistently worked in cancer is catching it early. Utilizing advanced technologies like genomics, transcriptomics, metabolomics, and artificial intelligence, coupled with continuous monitoring through tools like liquid biopsies, could revolutionize our ability to identify cancer at its earliest, most treatable stages.

A NEW PARADIGM FOR THE FUTURE OF CANCER FIGHT

The path forward, according to Raza, involves a radical reallocation of resources, shifting the majority from late-stage treatment development to early detection and prevention. While acknowledging the importance of ongoing research into cellular pathways and immunotherapies, she insists that the primary effort must be on identifying cancer before it becomes a deadly disease. This approach, she believes, is the key to truly winning the war on cancer and improving patient outcomes significantly.

Mentioned in This Episode

●Products

●Companies

●Organizations

●Books

●Concepts

●People Referenced

Common Questions

Dr. Raza was compelled to write her book 'The First Cell' after decades of experience as an oncologist, a cancer researcher, and a cancer widow. The ultimate catalyst was the tragic case of Andrew, a 22-year-old friend of her daughter, who died from an aggressive glioblastoma, highlighting the utter helplessness of current treatments against advanced cancers.

Topics

Health & Longevity Science & Mathematics Precision Medicine Cancer Treatment Medical Ethics Drug Development Cancer Research Healthcare Economics Medicine & Clinical Early Detection

Mentioned in this video

People

Harvey Preisler

Dr. Azra Raza's late husband, a cancer patient himself, whose battle with leukemia and death deeply influenced Raza's perspective and motivated her to write 'The First Cell'.

Judah Folkman

Doctor whose work on neovascularization led to the development of anti-VEGF drugs like Avastin.

Elizabeth Blackburn

Nobel laureate who shared the 2012 Hope Award in Cancer Research with Dr. Azra Raza.

Friedrich Nietzsche

Philosopher whose work 'Thus Spoke Zarathustra' is referenced by Dr. Raza to illustrate the idea of searching for fundamental truths in cancer research.

Katinka Matson

John Brockman's wife, who also encouraged Dr. Raza to write her book.

Azra Raza

Dr. Azra Raza is a professor of medicine and the director of the MDS Center at Columbia University. She is a practicing oncologist, cancer researcher, author of 'The First Cell', and an outspoken advocate for reconfiguring cancer research.

John Brockman

Dr. Raza's literary agent and friend, who encouraged her to write 'The First Cell'.

Judy Oaks

Dr. Raza's boss in pediatric oncology at Roswell Park who moved her to adult oncology due to her emotional struggles with pediatric cases.

Peter de Vries

Writer whose 1961 novel is referenced by Dr. Raza, containing a quote about medicine 'perfecting the art of prolonging disease,' highlighting the stagnation in leukemia treatment.

Thomas Kuhn

Philosopher of science whose idea about paradigm shifts ('if you want to change the paradigm, you have to show a better one') is cited by Dr. Raza regarding the need for new approaches in cancer research.

O. Henry

Oscar Wilde's former lover, Alfred Douglas, who tried to get Wilde to explain his famous poem quote, 'all men take the things they love.'

Emily Dickinson

American poet quoted by Dr. Raza multiple times during the discussion, highlighting her literary background and eloquent communication style.

Perry Marshall

Someone the host recently spoke with about the broken incentive structures in higher education, drawing parallels to healthcare.

Dorothy Parker

Writer quoted by Dr. Raza regarding the difficulty and gravity of writing a book.

Marty Makary

Author of 'The Price We Pay,' a book discussing the obscenity of healthcare costs in the U.S., specifically referenced regarding the financial ruin of cancer patients.

Otto Warburg

Scientist who made the first observation of anaerobic metabolism in cancer cells in 1921, highlighting that metabolic pathways in cancer have been studied for a long time.

Alfred Douglas

Oscar Wilde's boyfriend, who insisted Wilde explain the meaning of the refrain 'all men kill the things they love', leading to Wilde's explanation of self-delusion.

John Donne

Poet quoted by Dr. Raza to emphasize the inherent value of every human life with his poem 'No man is an island,' in response to questions about the cost-benefit analysis of cancer treatments.

Ted Schaeffer

Expert mentioned by the host in a previous podcast, who discusses the nuances of PSA testing for prostate cancer, advocating for PSA volume and velocity for better risk indication.

Oscar Wilde

Author of 'The Ballad of Reading Gaol,' quoted by Dr. Raza to illustrate the human tendency to destroy what we love through self-delusion, paralleling the misdirection in cancer research.

Arne Freeman

Dr. Raza's sister's boss at Roswell Park Cancer Institute who initially offered Dr. Raza a position.

Raj Atayawala

Expert mentioned by the host in a previous podcast, who discussed the limitations of mammography in cancer screening.

Books

Thus Spoke Zarathustra

Philosophical novel by Friedrich Nietzsche, referenced by Dr. Raza to metaphorically describe the search for foundational truths in cancer research.

No man is an island

Quotation from John Donne, used to underscore the intrinsic value of every human life.

The Price We Pay

Book by Marty Makary, recommended by Dr. Raza for its insights into the exorbitant and often exploitative costs within the American healthcare system, particularly for cancer patients.

The First Cell

Dr. Azra Raza's book, which offers a critical look at how medical research approaches cancer and its poor return on investment.

The Ballad of Reading Gaol

Poem by Oscar Wilde, quoted by Dr. Raza to reflect on the nature of self-delusion and its application to the misguided efforts in cancer research.

Products

m-Chip

An FDA-approved microfluidics-based chip that can test for biomarkers like PSA from a single drop of blood, envisioned by Dr. Raza as a tool for continuous, early detection of various cancers.

Gleevec

Targeted magic bullet drug, FDA approved in 2000, that cures chronic myeloid leukemia. It is highlighted as a fantastic success story in cancer treatment for a rare condition.

Grail

A company in the Bay Area developing similar liquid biopsy technologies to detect multiple cancers from a single blood sample, currently in Phase 2 trials.

Concepts

Melanoma

A type of skin cancer that has seen dramatic differences in survival rates due to advances in treatment, particularly immunotherapy.

Myelodysplastic Syndrome

A form of pre-leukemia in which Dr. Azra Raza is an expert.

Glioblastoma Multiforme

A highly malignant and unresectable brain tumor that Andrew died from, serving as a tragic example of the failure of current cancer treatments.

Multiple Myeloma

A hematologic cancer that has seen dramatic improvements in treatment, presenting a 'night and day difference' compared to earlier eras.

Lynch syndrome

A hereditary condition that increases the risk of certain cancers, mentioned in the context of checkpoint inhibitors being effective for cancers exhibiting specific mutations, even if they arise in organs like the pancreas.

Acute Promyelocytic Leukemia

One of the deadliest acute leukemias that can be cured with arsenic or Vitamin A analogs (ATRA). The discovery of its treatment pathways, initially observed by Chinese physicians, is discussed.

Acute Myeloid Leukemia

A form of leukemia in which Dr. Azra Raza is an expert. It is discussed as a disease where treatment has remained largely unchanged for decades.

Quality-Adjusted Life Year

A metric used by countries with public insurance to evaluate the cost-effectiveness of medical interventions, especially in cancer treatment, by quantifying the value of a life.

HeLa Cells

Famous immortalized cell line derived from cervical cancer, used extensively in cancer research but criticized for transcriptomic drift, making them less representative of original human cancers.

Chronic Myeloid Leukemia

A rare hematologic malignancy that was transformed by the targeted drug Gleevec, showing that one genetic change can be fixed with one magic bullet if caught early enough.

Hodgkin's Lymphoma

A type of lymphoma that can be cured with chemotherapy cocktails, illustrating a success story in oncology but one that is not easily replicated for other cancers.

CAR T-cell therapy

A type of immunotherapy where a patient's T-cells are engineered to fight cancer, applauded for its sophisticated science but criticized by Dr. Raza for its inability to distinguish between normal and cancer cells, leading to severe side effects and limited applicability.

Media

Mad Men

A television show mentioned as an example of historical widespread smoking that led to an increase in cancer incidence.

Drugs & Medications

Avastin

An anti-VEGF drug that was a 'blockbuster' for its novel approach to cancer treatment, extending median survival for metastatic colorectal cancer patients by about four months at a significant cost, sparking discussions on the value of life.

Daunorubicin

One of the two drugs, along with Citarabine, used in the '7 and 3' chemotherapy regimen for AML in 1977 and still used today.

Checkpoint Inhibitors

A class of immune therapies that unmask cancer cells to allow the body's immune system to recognize and attack them. While considered a significant advance, they also carry severe autoimmune side effects, questioning their overall benefit versus cost.

Citarabine

One of the two drugs, along with Daunorubicin, used in the '7 and 3' chemotherapy regimen for AML in 1977 and still used today.

ATRA

A Vitamin A analog used to cure acute promyelocytic leukemia, with its efficacy first noted by Chinese physicians before being confirmed in the West.

Kytruda

A checkpoint inhibitor drug, mentioned in the context of its high cost and the difficulty of justifying its value despite its effectiveness in some cancers.

Companies

Genentech

Pharmaceutical company that developed Avastin.

Toshiba

Company that announced they can detect 13 different cancers from one drop of blood in four hours for $180, illustrating the potential of new diagnostic technologies.

Organizations

Columbia University

The institution where Dr. Azra Raza is a professor of medicine and director of the MDS center.

Roswell Park Cancer Institute

Cancer institute in Buffalo, New York, where Dr. Raza began her work in pediatric oncology before moving to adult oncology and meeting Harvey Preisler.