New Molecular Pathways Found for Targeting Cancer Progression

In the ongoing fight against colorectal cancer (CRC)—the second leading cause of cancer mortality worldwide—recent research has provided significant insights into the molecular pathways that drive tumor progression and metastasis. When colon cancer is diagnosed early, survival rates are high, but once metastasis occurs, five-year survival rates fall below 10%, making the study of cancer spread critical.

Two distinct studies are highlighting novel approaches for Targeting Cancer Progression by identifying proteins and genes responsible for metastasis and early tumor strengthening.

One area of focus is preventing early-stage tumors from acquiring multiple mutations and becoming stronger. Researchers led by Nan Gao, PhD, are investigating the protein Cdc42-v2, which acts like a "switch" that, when mistakenly "turned on" in CRC cells in the intestines, helps tumors grow. Cdc42-v2 is normally found in the brain.

The goal of this research is to find a way to "turn off" this protein to limit cancer progression and spread. Gao's team discovered that intestinal cancer stem cells in mice require Cdc42-v2 to thrive, and eliminating or deactivating the protein halts tumor growth. These findings offer hope that treatments can be developed to target Cdc42-v2 and stop CRC before it truly "gets started".

Separately, research led by Christopher J. Lengner and M. Andrés Blanco used the gene-editing technology CRISPR and organoid models to identify genes that actively suppress metastasis. The team looked for genes that, when disrupted, caused the cancer to spread.

This systematic screening identified two crucial metastasis suppressors: Ctnna1 (alpha-catenin) and Bcl2l13 (BCL-Rambo).

Ctnna1 regulates traditional metastasis mechanisms by helping to keep cells "locked in," preventing them from crawling away from their neighbors and invading surrounding tissues. BCL2L13, on the other hand, promotes a specific type of cell death that is triggered when epithelial cells detach from their tissue layer, thus preventing these cells from surviving in the wrong place. Metastatic cells may suppress BCL2L13 to survive after leaving the primary tumor.

This innovative approach combined introducing mutations to create lab-grown colon tumoroids and then evaluating metastasis in an in vivo model, confirming that large-scale genetic screening can effectively identify key regulators of metastasis comparable to human CRC. Identifying genes that promote metastasis is a next step for researchers, as these would represent ideal targets for future therapeutic intervention.

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🔖 Sources

Two genes found to suppress colorectal cancer spread in preclinical models

Targeting a Protein “Turned on” by Mistake May Stop Colon Cancer

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Keywords: Targeting Cancer Progression

Targeting Cancer Progression

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