本期播客由斯坦福大学放射肿瘤学教授Max Diehn主讲，深入探讨了液体活检在癌症检测中的应用。Max详细介绍了液体活检的历史、现状和未来发展，包括其作为癌症检测工具的潜力，以及如何通过非侵入性的血液检测来检测肿瘤细胞释放到血液中的DNA/RNA。节目中，Max解释了细胞游离DNA/RNA特征、甲基化模式，以及突变信息的重要性，并展望了液体活检在癌症筛查中的未来。此外，还讨论了血液癌症筛查的历史、测试的预测价值、低剂量CT扫描的局限性等关键问题。

🩸 液体活检的兴起：Max Diehn教授分享了他对液体活检的理解，液体活检是一种通过血液检测来检测癌症的技术，旨在通过检测血液中的肿瘤DNA/RNA来早期发现癌症。

🔬 液体活检的原理：液体活检通过检测血液中的细胞游离DNA（cfDNA）和细胞游离RNA（cfRNA）来工作，这些物质是由肿瘤细胞释放到血液中的。通过分析这些物质的特征，如突变、甲基化模式等，可以推断是否存在癌症。

💡 液体活检的优势与挑战：液体活检具有非侵入性、可重复性等优势，但目前仍面临一些挑战，例如灵敏度和特异性问题。节目中，Max讨论了现有液体活检测试的局限性，以及如何提高其准确性。

🚀 液体活检的未来展望：Max对液体活检的未来充满信心，认为它有望成为一种更全面的癌症筛查工具。他讨论了如何通过液体活检实现更早的癌症检测，从而改善患者的预后。

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Max Diehn is a Professor of Radiation Oncology at Stanford and a clinical radiation oncologist specializing in lung cancer. Max’s research focuses on developing novel methods for detecting circulating tumor DNA in the blood of cancer patients and on elucidating the molecular pathways and genes associated with cancer. His interests also include uncovering biomarkers that can predict patient survival, responses to therapy, and disease recurrence. In this packed episode, Max discusses the history of blood-based cancer screening and the importance of understanding the predictive value of tests—sensitivity, specificity, negative predictive value, positive predictive value – and how these metrics play into cancer screening. Max then goes in depth on the topic of liquid biopsies, including the history, current landscape, and possible future of liquid biopsies as a cancer detection tool. He discusses how these non-invasive blood tests can detect DNA/RNA from tumor cells released into the blood as well as the different methods one can use to predict if a cancer is present. He gets granular on the topic of cell-free DNA/RNA signature, methylation patterns, and the importance of knowing mutation information, and he ends with a discussion on the exciting future of liquid biopsies and how we can possibly get to the panacea of cancer screening.

We discuss:

Max’s training that planted the seeds for development of liquid biopsies [4:30]; Max’s decision to specialize in radiation oncology [11:45]; A culture at Stanford that values research and physician scientists [17:00]; The motivation to develop liquid biopsies [19:15]; History of blood-based cancer screening and understanding the predictive value of tests [25:30]; Current state of lung cancer and the need for better screening [32:45]; Low-dose CT scans: an important tool for managing lung cancer but with limitations [42:00]; Using liquid biopsies to identify circulating tumor cells [47:00]; Liquid biopsy research moves from circulating tumor cells to cell-free DNA [1:03:00]; Zeroing-in on circulating tumor DNA in cell-free DNA [1:10:48]; Cell-free RNA and Max’s vision for cancer detection from a blood sample [1:22:00]; Methylation patterns and other informative signatures found in DNA [1:24:30]; Mutation-based methods of liquid biopsies [1:26:30]; Understanding the sensitivity and specificity of a diagnostic test [1:30:30]; Existing clinical liquid biopsy tests and their limitations [1:37:30]; The future of liquid biopsies [1:44:00]; How we get to the panacea of cancer screening [1:52:00]; More.

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