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

KEYPOINTS

• 01

  Raza argues that age-adjusted cancer mortality is essentially where it was in 1930

  Peter usually says cancer mortality hasn't changed since about 1970. Raza goes further. She says the roughly 27–30% decline over the last 30 years followed a 30-year rise driven by smoking, so the fall mostly tracks the drop in smoking. In her words, 'otherwise we are really at square one.' She compares herself to Nietzsche's man with a lamp at noon, except she is 'looking for an adult in the room.'

• 02

  Most cures still come from 'slash, poison, burn,' and only in early disease

  Raza's breakdown: of newly diagnosed cancers, about 68% are cured, overwhelmingly with surgery, chemotherapy and radiation. The 32% who present with advanced disease mostly can't be cured with those same tools. She takes this as the best evidence that the only reliable lever is catching cancer early. Some of the first chemotherapy agents came out of chemical weapons research, and she gave all three of the original drugs to her own husband.

• 03

  Real breakthroughs are real but rare

  Gleevec for CML and GI stromal tumors proved targeted therapy can work, but those are rare cancers, and Peter doubts it has moved overall mortality even 1%. Melanoma survival is dramatically better with checkpoint inhibitors. Still, Raza estimates all such successes together account for under 10% of cancers. Her question is whether they reflect the 'quarter of a trillion dollars' invested. She is clear that this research should continue.

• 04

  95% of experimental cancer drugs fail, and Raza says many of the 5% shouldn't have passed

  In her account, the 'winners' often extend survival by a few months in only 20–30% of patients. Approvals often rest on progression-free survival: if the tumor isn't seen to grow for an extra two and a half months but the patient dies at the same time, the drug can still be approved and earn billions. Peter adds that a 'partial response' has a somewhat arbitrary definition and that durability is rarely discussed.

• 05

  The core scientific problem, in her view, is the preclinical model

  Raza blames the failure rate on reductionist testing platforms such as cell lines, 2D and 3D cultures, and genetically engineered or immune-compromised mice. She says she supports animal research for biology, but not for drug development, because what a drug does in a mouse is only true for mice. She would not even rely on animals for safety. She points to the FDA's phase zero design, which starts humans at 1/500th of a dose and escalates.

• 06

  New drugs often cost far more for small gains, with ruinous consequences for patients

  Her figures: 42% of newly diagnosed cancer patients will be financially ruined by the second year, and 50% of women with breast cancer are pursued by collection agencies. Peter recalls that Avastin in metastatic colorectal cancer added about four months of median survival at roughly $100,000, which led some publicly funded systems to rely on quality-adjusted life years. Peter flags that his Avastin details may not be exact.

• 07

  Good intentions slowly produced a broken system

  Raza uses the frog-in-slowly-heating-water image: each step began with good intentions. Peter adds that publication as a promotion metric fuels a 'cottage industry' of low-quality journals and irreproducible studies. He also says that by his own analysis from about five years earlier, slightly more than half of global oncology research money ran through the NCI after Nixon's war on cancer, though he notes he could be a little wrong.

• 08

  Her proposed solution is aggressive early detection, monitored continuously

  Raza argues that mammograms and PSA failing on their own doesn't prove early detection fails. She wants genomics, transcriptomics, proteomics, metabolomics and imaging combined with AI, with up to '50 tests if we have to,' read continuously rather than once a year. Peter frames it as three rules: don't get cancer, screen smartly, and treat when tumors are in the millions rather than billions of cells. He estimates lifestyle changes could cut cancer risk 30–50%, based on his reading of the literature.

• 09

  Powerful late-stage therapies should move earlier

  She calls current treatment 'paleolithic,' quoting the line about beating a dog with a baseball bat to get rid of its fleas. She notes that whole industries exist just to manage CAR-T side effects. She says such therapies should be developed, but used when tumor burden is low.