Sendurai Mani, Associate Director of Translational Oncology, Dean’s Chair of Translational Oncology, and Professor of Medicine at Brown University, and Co-Founder and CSO of Iylon Precision Oncology, shared a post on LinkedIn:
“𝗥𝗲𝗳𝗹𝗲𝗰𝘁𝗶𝗼𝗻𝘀 𝗼𝗻 𝗘𝗠𝗧, 𝗦𝘁𝗲𝗺𝗻𝗲𝘀𝘀, 𝗮𝗻𝗱 𝗖𝗲𝗹𝗹𝘂𝗹𝗮𝗿 𝗛𝗲𝘁𝗲𝗿𝗼𝗴𝗲𝗻𝗲𝗶𝘁𝘆
Many years ago, I discovered that activation of the epithelial-to-mesenchymal transition (EMT) program can endow cancer cells with stem cell–like properties. You can hear Bob Weinberg’s reflections on how this idea emerged and evolved. This finding had a profound impact; this paper has now been 𝗰𝗶𝘁𝗲𝗱 𝗼𝘃𝗲𝗿 𝟭𝟬,𝟬𝟬𝟬 𝘁𝗶𝗺𝗲𝘀 (𝗚𝗼𝗼𝗴𝗹𝗲 𝗦𝗰𝗵𝗼𝗹𝗮𝗿).
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, ‘𝘿𝙤𝙚𝙨 𝙀𝙈𝙏 𝙥𝙧𝙤𝙙𝙪𝙘𝙚 𝙖 𝙨𝙞𝙣𝙜𝙡𝙚 𝙩𝙮𝙥𝙚 𝙤𝙛 𝙘𝙚𝙡𝙡, 𝙤𝙧 𝙢𝙪𝙡𝙩𝙞𝙥𝙡𝙚 𝙨𝙪𝙗𝙥𝙤𝙥𝙪𝙡𝙖𝙩𝙞𝙤𝙣𝙨, 𝙨𝙤𝙢𝙚 𝙩𝙝𝙖𝙩 𝙖𝙧𝙚 𝙥𝙪𝙧𝙚𝙡𝙮 𝙢𝙚𝙨𝙚𝙣𝙘𝙝𝙮𝙢𝙖𝙡, 𝙖𝙣𝙙 𝙤𝙩𝙝𝙚𝙧𝙨 𝙩𝙝𝙖𝙩 𝙖𝙧𝙚 𝙗𝙤𝙩𝙝 𝙢𝙚𝙨𝙚𝙣𝙘𝙝𝙮𝙢𝙖𝙡 𝙖𝙣𝙙 𝙨𝙩𝙚𝙢-𝙡𝙞𝙠𝙚?’ 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:
- 𝙒𝙝𝙚𝙣 𝙘𝙖𝙣𝙘𝙚𝙧 𝙘𝙚𝙡𝙡𝙨 𝙪𝙣𝙙𝙚𝙧𝙜𝙤 𝙀𝙈𝙏, 𝙖𝙡𝙡 𝙜𝙖𝙞𝙣 𝙢𝙚𝙨𝙚𝙣𝙘𝙝𝙮𝙢𝙖𝙡 𝙘𝙝𝙖𝙧𝙖𝙘𝙩𝙚𝙧𝙞𝙨𝙩𝙞𝙘𝙨, 𝙗𝙪𝙩 𝙤𝙣𝙡𝙮 𝙖 𝙨𝙪𝙗𝙨𝙚𝙩 𝙖𝙘𝙦𝙪𝙞𝙧𝙚𝙨 𝙨𝙩𝙚𝙢𝙣𝙚𝙨𝙨.
- 𝙀𝙫𝙚𝙧𝙮 𝙨𝙩𝙚𝙢-𝙡𝙞𝙠𝙚 𝙘𝙚𝙡𝙡 𝙙𝙞𝙨𝙥𝙡𝙖𝙮𝙨 𝙢𝙚𝙨𝙚𝙣𝙘𝙝𝙮𝙢𝙖𝙡 𝙩𝙧𝙖𝙞𝙩𝙨, 𝙗𝙪𝙩 𝙣𝙤𝙩 𝙚𝙫𝙚𝙧𝙮 𝙢𝙚𝙨𝙚𝙣𝙘𝙝𝙮𝙢𝙖𝙡 𝙘𝙚𝙡𝙡 𝙜𝙖𝙞𝙣𝙨 𝙨𝙩𝙚𝙢𝙣𝙚𝙨𝙨.
- 𝙎𝙩𝙚𝙢 𝙘𝙚𝙡𝙡 𝙥𝙧𝙤𝙥𝙚𝙧𝙩𝙞𝙚𝙨 𝙧𝙚𝙦𝙪𝙞𝙧𝙚 𝙘𝙚𝙡𝙡 𝙙𝙞𝙫𝙞𝙨𝙞𝙤𝙣, 𝙬𝙝𝙚𝙧𝙚𝙖𝙨 𝙢𝙚𝙨𝙚𝙣𝙘𝙝𝙮𝙢𝙖𝙡 𝙩𝙧𝙖𝙞𝙩𝙨 𝙘𝙖𝙣 𝙖𝙧𝙞𝙨𝙚 𝙨𝙞𝙢𝙥𝙡𝙮 𝙛𝙧𝙤𝙢 𝙚𝙭𝙥𝙤𝙨𝙪𝙧𝙚 𝙩𝙤 𝙀𝙈𝙏-𝙞𝙣𝙙𝙪𝙘𝙞𝙣𝙜 𝙨𝙞𝙜𝙣𝙖𝙡𝙨, 𝙬𝙞𝙩𝙝𝙤𝙪𝙩 𝙥𝙧𝙤𝙡𝙞𝙛𝙚𝙧𝙖𝙩𝙞𝙤𝙣.
- 𝘼𝙡𝙩𝙚𝙧𝙣𝙖𝙩𝙞𝙫𝙚 𝙨𝙥𝙡𝙞𝙘𝙞𝙣𝙜 𝙧𝙚𝙜𝙪𝙡𝙖𝙩𝙚𝙨 𝙩𝙝𝙚 𝙖𝙘𝙦𝙪𝙞𝙨𝙞𝙩𝙞𝙤𝙣 𝙤𝙛 𝙨𝙩𝙚𝙢𝙣𝙚𝙨𝙨 𝙞𝙣 𝙖 𝙘𝙚𝙡𝙡 𝙙𝙞𝙫𝙞𝙨𝙞𝙤𝙣–𝙙𝙚𝙥𝙚𝙣𝙙𝙚𝙣𝙩 𝙢𝙖𝙣𝙣𝙚𝙧.
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 from Sendurai Mani.