Sendurai Mani, Associate Director of Translational Oncology, Deanโs Chair of Translational Oncology, and Professor of Medicine at Brown University, and Co-Founder and CSO of Iylon Precision Oncology, shared a post onย LinkedIn:
“๐ฅ๐ฒ๐ณ๐น๐ฒ๐ฐ๐๐ถ๐ผ๐ป๐ ๐ผ๐ป ๐๐ ๐ง, ๐ฆ๐๐ฒ๐บ๐ป๐ฒ๐๐, ๐ฎ๐ป๐ฑ ๐๐ฒ๐น๐น๐๐น๐ฎ๐ฟ ๐๐ฒ๐๐ฒ๐ฟ๐ผ๐ด๐ฒ๐ป๐ฒ๐ถ๐๐
Many years ago, I discovered that activation of the epithelial-to-mesenchymal transition (EMT) program can endow cancer cells with stem cellโlike properties. You can hear Bob Weinbergโs reflections on how this idea emerged and evolved. This finding had a profound impact; this paper has now been ๐ฐ๐ถ๐๐ฒ๐ฑ ๐ผ๐๐ฒ๐ฟ ๐ญ๐ฌ,๐ฌ๐ฌ๐ฌ ๐๐ถ๐บ๐ฒ๐ (๐๐ผ๐ผ๐ด๐น๐ฒ ๐ฆ๐ฐ๐ต๐ผ๐น๐ฎ๐ฟ).
In many carcinomas, we see cells with mesenchymal morphology that are not highly aggressive; similarly, when EMT is experimentally induced, not every cell gains stem-like traits. This observation raises a deeper biological question: Is there heterogeneity within the EMT-induced population?
In other words, ‘๐ฟ๐ค๐๐จ ๐๐๐ ๐ฅ๐ง๐ค๐๐ช๐๐ ๐ ๐จ๐๐ฃ๐๐ก๐ ๐ฉ๐ฎ๐ฅ๐ ๐ค๐ ๐๐๐ก๐ก, ๐ค๐ง ๐ข๐ช๐ก๐ฉ๐๐ฅ๐ก๐ ๐จ๐ช๐๐ฅ๐ค๐ฅ๐ช๐ก๐๐ฉ๐๐ค๐ฃ๐จ, ๐จ๐ค๐ข๐ ๐ฉ๐๐๐ฉ ๐๐ง๐ ๐ฅ๐ช๐ง๐๐ก๐ฎ ๐ข๐๐จ๐๐ฃ๐๐๐ฎ๐ข๐๐ก, ๐๐ฃ๐ ๐ค๐ฉ๐๐๐ง๐จ ๐ฉ๐๐๐ฉ ๐๐ง๐ ๐๐ค๐ฉ๐ ๐ข๐๐จ๐๐ฃ๐๐๐ฎ๐ข๐๐ก ๐๐ฃ๐ ๐จ๐ฉ๐๐ข-๐ก๐๐ ๐?’ Understanding this will help diagnose and selectively target these aggressive stem-like cancer cells.
This question was explored brilliantly by Petra den Hollander, and members of my team uncovered:
- ๐๐๐๐ฃ ๐๐๐ฃ๐๐๐ง ๐๐๐ก๐ก๐จ ๐ช๐ฃ๐๐๐ง๐๐ค ๐๐๐, ๐๐ก๐ก ๐๐๐๐ฃ ๐ข๐๐จ๐๐ฃ๐๐๐ฎ๐ข๐๐ก ๐๐๐๐ง๐๐๐ฉ๐๐ง๐๐จ๐ฉ๐๐๐จ, ๐๐ช๐ฉ ๐ค๐ฃ๐ก๐ฎ ๐ ๐จ๐ช๐๐จ๐๐ฉ ๐๐๐ฆ๐ช๐๐ง๐๐จ ๐จ๐ฉ๐๐ข๐ฃ๐๐จ๐จ.
- ๐๐ซ๐๐ง๐ฎ ๐จ๐ฉ๐๐ข-๐ก๐๐ ๐ ๐๐๐ก๐ก ๐๐๐จ๐ฅ๐ก๐๐ฎ๐จ ๐ข๐๐จ๐๐ฃ๐๐๐ฎ๐ข๐๐ก ๐ฉ๐ง๐๐๐ฉ๐จ, ๐๐ช๐ฉ ๐ฃ๐ค๐ฉ ๐๐ซ๐๐ง๐ฎ ๐ข๐๐จ๐๐ฃ๐๐๐ฎ๐ข๐๐ก ๐๐๐ก๐ก ๐๐๐๐ฃ๐จ ๐จ๐ฉ๐๐ข๐ฃ๐๐จ๐จ.
- ๐๐ฉ๐๐ข ๐๐๐ก๐ก ๐ฅ๐ง๐ค๐ฅ๐๐ง๐ฉ๐๐๐จ ๐ง๐๐ฆ๐ช๐๐ง๐ ๐๐๐ก๐ก ๐๐๐ซ๐๐จ๐๐ค๐ฃ, ๐ฌ๐๐๐ง๐๐๐จ ๐ข๐๐จ๐๐ฃ๐๐๐ฎ๐ข๐๐ก ๐ฉ๐ง๐๐๐ฉ๐จ ๐๐๐ฃ ๐๐ง๐๐จ๐ ๐จ๐๐ข๐ฅ๐ก๐ฎ ๐๐ง๐ค๐ข ๐๐ญ๐ฅ๐ค๐จ๐ช๐ง๐ ๐ฉ๐ค ๐๐๐-๐๐ฃ๐๐ช๐๐๐ฃ๐ ๐จ๐๐๐ฃ๐๐ก๐จ, ๐ฌ๐๐ฉ๐๐ค๐ช๐ฉ ๐ฅ๐ง๐ค๐ก๐๐๐๐ง๐๐ฉ๐๐ค๐ฃ.
- ๐ผ๐ก๐ฉ๐๐ง๐ฃ๐๐ฉ๐๐ซ๐ ๐จ๐ฅ๐ก๐๐๐๐ฃ๐ ๐ง๐๐๐ช๐ก๐๐ฉ๐๐จ ๐ฉ๐๐ ๐๐๐ฆ๐ช๐๐จ๐๐ฉ๐๐ค๐ฃ ๐ค๐ ๐จ๐ฉ๐๐ข๐ฃ๐๐จ๐จ ๐๐ฃ ๐ ๐๐๐ก๐ก ๐๐๐ซ๐๐จ๐๐ค๐ฃโ๐๐๐ฅ๐๐ฃ๐๐๐ฃ๐ฉ ๐ข๐๐ฃ๐ฃ๐๐ง.
These insights remind us that biology is rarely binary. Even within this EMT pathway, multiple cell states exist, each with distinct potential for tumor evolution and therapy resistance. Understanding this diversity is the key to designing more precise and effective cancer treatments.”
More fromย Sendurai Mani.