On November 23, 2023 Perpetual Medicines reported in preclinical studies using laboratory models, manipulating β-catenin levels or activity has demonstrated a significant impact on tumor growth. Inhibition of β-catenin signaling has been shown to suppress the growth of cancer cells, providing a solid rationale for developing drugs that specifically target this pathway.
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ß-catenin was discovered in the early 1980’s based on its roles in cytoskeleton structure and signaling. ß-catenin is evolutionarily conserved from worms to fruit flies to humans and is a pivotal factor in development and tissue homeostasis, cell renewal, and regeneration. Disruption of the pathway by germline and acquired mutations has implicated ß-catenin as a key driver of oncogenesis.
There have been over 40 licensing/collaboration deals in the WNT pathway in the last ten years, and 11 disclosed deal terms comprising an aggregate value of $3.27B. ß-catenin is a critical node and driver of the WNT pathway and is an attactive target for cancer drug discovery.
-Kerry Blanchard, M.D., Ph.D., Co-founder, President, CEO"
β-catenin, a protein crucial for cell communication and development, has emerged as a promising drug target in the battle against cancer. Significant strides have been made in understanding the role of β-catenin in cancer development. Recurring genetic mutations activate β-catenin, underscoring its pivotal role in driving tumor growth. In addition to genetic validation, several other lines of evidence support β-catenin as a compelling target for anti-cancer drugs:
1 Correlation with Tumor Aggressiveness
High levels of β-catenin activity have been correlated with more aggressive tumor behavior and poorer prognosis in multiple cancer types. This suggests that targeting β-catenin could potentially inhibit the growth and spread of cancer cells.
2 Preclinical Models
In preclinical studies using laboratory models, manipulating β-catenin levels or activity has demonstrated a significant impact on tumor growth. Inhibition of β-catenin signaling has been shown to suppress the growth of cancer cells, providing a solid rationale for developing drugs that specifically target this pathway.
3 Association with Cancer Stem Cells
β-catenin plays a crucial role in maintaining cancer stem cells, which are thought to drive tumor initiation, progression, and resistance to therapy. Targeting β-catenin may therefore disrupt these cancer stem cells, potentially improving the efficacy of anti-cancer treatments.
4 Clinical Correlations:
In some clinical studies, elevated β-catenin expression has been associated with resistance to conventional cancer therapies. Combining traditional treatments with β-catenin-targeted drugs could enhance therapeutic outcomes and overcome resistance.
The WNT pathway has been fertile ground for partnerships over the last few decades primarily based on the validation status of the target. Over the last decade, more than $3.27B of deals have been focused on the pathway. Most projects have focused on the upstream components of the WNT pathway: requisite components of WNT ligand release (porcupine), WNT ligand blockers, WNT receptor inhibitors, and intracellular WNT pathway blockers. These approaches inhibit the canonical WNT pathway as well as the non-canonical pathway leading to significant on-target toxicity. But the willingness of multinational pharmaceutical companies to still invest in approaches to inhibit the WNT pathway highlight the importance of this pathway.
Previous drug discovery efforts have laid the groundwork for potential breakthroughs, with researchers exploring compounds that can modulate β-catenin activity, however, none of these efforts have led to an approved drug targeting β-catenin. Recent advances in peptide therapeutics have made β-catenin an approachable target via blocking intracellular protein:protein interactions.We believe the advances in peptide-based modalities for blocking essential protein:protein interactions opens a new world of opportunities in controlling WNT activation.An effective medicine that targets β-catenin would be a beacon of hope in the quest for more effective and targeted cancer therapies.
(Press release, Perpetual Medicines, NOV 23, 2023, View Source [SID1234661245])