cover of episode The future of liquid biopsy

The future of liquid biopsy

2025/2/28
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A
Ash Alizadeh
D
Daniel Kim
R
Russ Altman
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@Russ Altman : 本期节目讨论了液体活检技术,一种通过血液样本检测癌症的新技术,它正在革命性地改变癌症检测和治疗跟踪的方式。液体活检目前主要用于治疗后的跟踪,检测血液中是否仍有癌症DNA,并在免疫肿瘤学领域有新的应用前景。 @Ash Alizadeh : 液体活检通过体液非侵入性地获取组织信息,可以用于检测局部癌症,如肺癌或肝癌。最初的应用是在产前诊断和器官排斥检测中。癌症DNA与正常DNA的差异可以通过突变、结构改变和表观遗传变化来检测。液体活检技术通过检测血液中的DNA差异来识别癌症,并正在向非突变分子和RNA检测方向发展。RNA可以作为实时肿瘤标志物,揭示肿瘤的活跃过程和药物耐药性。肿瘤知情策略通过初始肿瘤样本创建个性化标记,用于监测癌症复发。尽管癌症会进化,核心突变仍然可以被检测到。DNA、RNA和甲基化的稳定性不同,DNA是最稳定的。 @Daniel Kim : 提出了关于早期癌症检测的液体活检技术是否可以在未来几年内实现的问题。 Ash Alizadeh: 液体活检技术在早期癌症检测中的表现令人失望,尚未证明其临床价值。目前液体活检技术可以用于监测CAR T细胞疗法的效果,并可以帮助理解肿瘤微环境,从而开发新的治疗方法。通过研究霍奇金淋巴瘤,我们发现液体活检可以更有效地诊断和基因分析这种癌症,因为血液中肿瘤来源的DNA比例远高于肿瘤组织。我们还发现,肿瘤微环境的差异可能与癌症亚型有关,这为开发新的治疗方法提供了可能性。我们开发了一种名为EpicSeq的方法,可以从DNA片段组学推断基因表达,从而识别肿瘤微环境中的差异。这表明,未来的治疗策略可能不仅针对癌细胞本身,也可能破坏支持癌症的微环境。

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This chapter introduces the concept of liquid biopsy, a non-invasive method of disease diagnosis using bodily fluids like blood, urine, or cerebrospinal fluid. It contrasts traditional biopsy methods and highlights the ability of liquid biopsies to detect localized cancers and monitor treatment effectiveness. The chapter details the different types of DNA differences used for cancer detection, including genetic mutations, structural alterations, and epigenetic changes.
  • Liquid biopsy accesses tissue through bodily fluids, avoiding invasive procedures.
  • It detects localized cancers in blood samples.
  • DNA differences, including mutations, copy number aberrations, and methylation, are used for detection.

Shownotes Transcript

Physician Ash Alizadeh has seen the future of disease diagnosis and monitoring. It is coursing through every patient’s veins. Traditionally, biopsies have required invasively gathering tissue – from a lung, a liver, or a fetus. Now it’s possible to look for disease without surgery. The DNA is sitting there in the bloodstream, Alizadeh tells host Russ Altman, as they preview the age of liquid biopsies on this episode of Stanford Engineering’s The Future of Everything podcast.

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Chapters:

(00:00:00) Introduction

Russ Altman introduces guest Ash Alizadeh, a faculty member at Stanford University in Oncology and Medicine.

(00:03:39) What is a Liquid Biopsy?

Accessing tissues non-invasively using bodily fluids.

(00:04:31) Detecting Cancer with Liquid Biopsies

How localized cancers can be detected through blood samples.

(00:06:32) The Science Behind Cancer DNA Detection

The differences between normal and cancer DNA

(00:09:51) How Liquid Biopsy Technology Works

The technologies behind detecting cancer-related DNA differences.

(00:12:36) Advances in Liquid Biopsy

New detection approaches using non-mutant molecules and RNA.

(00:14:10) RNA as a Real-Time Tumor Marker

How RNA reveals active tumor processes and drug resistance.

(00:15:55) Tracking Cancer Reccurence

Using tumor-informed panels to monitor cancer recurrence.

(00:16:28)  Adapting to Tumor Evolution

Why core mutations remain detectable despite cancer changes.

(00:17:57) Stability of DNA, RNA, and Methylation

Comparing durability and reliability of different biomarkers.

(00:20:49) Listener Question: Early Cancer Detection

Daniel Kim asks about pre-cancer detection and its potential impact.

(00:24:44) Liquid Biopsy in Immunotherapy

Using liquid biopsy to track and improve immune-based treatments.

(00:27:35) Monitoring CAR T-Cell Therapy

How liquid biopsy helps assess immune cell expansion.

(00:32:02) EPIC-Seq: Inferring RNA from DNA

Using DNA fragmentation to predict gene expression in tumors.

(00:34:49) Targeting Tumor Support Systems

Treatment strategies disrupting the tumor microenvironment.

(00:35:52) Conclusion

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