Colorectal Cancer & The Plasticity Problem: How Cancer Cells Outsmart Treatment

Metastasis in colorectal cancer is driven by cellular plasticity—cancer cells’ ability to adapt, survive, and thrive in new environments. Think of plasticity as the way these cells “shape-shift” to become even more dangerous.

Mechanisms of Plasticity Driving Metastasis in CRC:

1️⃣ Epithelial-to-Mesenchymal Transition (EMT) & Mesenchymal-to-Epithelial Transition (MET)
* EMT gives cancer cells mobility—letting them invade the bloodstream and reach new destinations.
* MET allows them to re-establish themselves at these new sites and grow.

2️⃣ Stemness & Dedifferentiation
* Cancer cells gain stem-like properties, making them highly resistant and allowing them to survive under harsh conditions.
* They undergo dedifferentiation, which allows them to switch back to a more adaptable, primitive state—keeping them flexible and ready to resist treatment.

3️⃣ Immune Evasion & Microenvironment Adaptation
* Plasticity helps cancer cells evade immune detection.
* These cells adapt to new microenvironments like the liver or lungs, making them incredibly difficult to target and destroy.

Here’s the Problem: Current therapies struggle to tackle the adaptability of cancer cells, which leads to recurrenceand progression. In fact, some traditional treatments may even increase this plasticity, making cancer cells more aggressive.

At the Williams Cancer Institute, we believe in breaking the mold, challenging conventional wisdom, and innovating treatment strategies to finally bring cellular plasticity under control. It’s time to turn adaptability against cancer, not let it dictate the terms.

➡️ Click the link in my bio to learn more about our approach to colorectal cancer and access resources to help you make empowered decisions.

Supporting Evidence:
* Moorman AR, Benitez EK, Cambuli F, Jiang Q, Mahmoud A, Lumish M, Hartner S, Balkaran S, Bermeo J, Asawa S, Firat C, Saxena A, Wu F, Luthra A, Burdziak C, Xie Y, Sgambati V, Luckett K, Li Y, Yi Z, Masilionis I, Soares K, Pappou E, Yaeger R, Kingham P, Jarnagin W, Paty P, Weiser MR, Mazutis L, D'Angelica M, Shia J, Garcia-Aguilar J, Nawy T, Hollmann TJ, Chaligné R, Sanchez-Vega F, Sharma R, Pe'er D, Ganesh K. Progressive plasticity during colorectal cancer metastasis. Nature. 2024 Oct 30. doi: 10.1038/s41586-024-08150-0.

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