# Pan-cancer Myc modulator that targets Myc-α-tubulin interaction to drive selective mitotic catastrophe

## TL;DR

A new drug called DL78 selectively targets cancer cells by disrupting a key protein interaction, causing cancer-specific cell death without harming healthy cells.

## Contribution

DL78 is a novel Myc modulator that induces mitotic catastrophe by targeting the Myc-α-tubulin interaction, offering a new therapeutic strategy for cancer.

## Key findings

- DL78 inhibits growth in nine cancer types and reduces tumor burden in a platinum-resistant ovarian cancer model without toxicity.
- DL78 preferentially targets MYC-overexpressing, chromosomally unstable cancer cells.
- DL78 causes mitotic arrest and apoptosis by disrupting Myc’s interaction with α-tubulin.

## Abstract

MYC overexpression is a well-established cancer vulnerability, yet direct therapeutic targeting of Myc remains a challenge. Here, we identify DL78 as a potent antimitotic agent with selective anticancer activity through its regulation of Myc. DL78 demonstrated broad efficacy by inhibiting growth across nine cancer types and significantly reducing tumor burden in an in vivo model of platinum-resistant high-grade serous ovarian cancer, with no overt toxicity. DL78 preferentially targets chromosomally unstable, MYC-overexpressing cancer cells, a hallmark of high-grade serous ovarian cancer. Mechanistically, DL78 exploits Myc’s role in mitotic entry by disrupting its interaction with α-tubulin, leading to sustained mitotic arrest, mitotic catastrophe, and apoptosis while sparing nonmalignant cells. This study establishes a novel paradigm for Myc-targeted therapy by introducing DL78, which induces cancer-selective mitotic catastrophe by disrupting Myc’s interaction with α-tubulin rather than its transcriptional activity.

The online version contains supplementary material available at 10.1038/s41598-025-22011-4.