Designing a tumor-selective ENPP1 inhibitor

Biochemist Lingyin Li survived breast cancer at just 30 and now works to harness the human immune system to fight cancers that have long evaded treatment. T cells, she says, are powerful cancer killers, but they can be oblivious. She and her lab colleagues have discovered a masking enzyme that squelches the immune system’s “danger signals” and are now developing drugs to block that enzyme. She likens her work to an arms race between cancer and immunotherapy. “The cancers are not getting smarter, but we are,” Li tells host Russ Altman on this episode of Stanford Engineering’s The Future of Everything podcast.

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Episode Reference Links:

• Stanford Profile: Lingyin Li

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• Episode Transcripts >>> The Future of Everything Website
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Chapters:

(00:00:00) Introduction

Russ Altman introduces guest Lingyin Li, a professor of biochemistry at Stanford University.

(00:03:38) Research Motivation

Lingyin explains how her breast cancer diagnosis inspired her research.

(00:04:31) How T-Cells Work

T-cell mechanisms and why they struggle to reach solid tumors.

(00:05:38) Immune System Overview

Innate and adaptive immunity and how mutations make cancer recognizable.

(00:07:28) Awakening the Immune System

Efforts to stimulate innate immune cells to detect and expose tumors.

(00:10:54) The Cancer Signal

Discovery of cancer-derived DNA signals that alert the immune system.

(00:13:01) Cancer’s Evasion Mechanism

How tumors destroy immune signals to hide from detection.

(00:14:26) ENPP1 Enzyme

Identification of ENPP1 as the enzyme enabling immune evasion.

(00:15:22) Balancing Immunity and Safety

Role of ENPP1 in autoimmunity and the challenge of targeting it safely.

(00:19:30) ENPP1 Inhibitors

Development of molecules to block ENPP1 and enhance immune signaling.

(00:24:55) Preclinical Findings

The promising results against aggressive solid tumors in animal studies

(00:28:05) From Lab to Clinic

The progress toward FDA approval and preparation for human testing.

(00:31:04) Future In a Minute

Rapid-fire Q&A: innovation, collaboration, and the outlook for cancer treatment.

(00:33:14) Conclusion

Connect With Us:

Episode Transcripts >>> The Future of Everything Website

Connect with Russ >>> Threads / Bluesky / Mastodon

Connect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook

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