MYC as a Target for Cancer Treatment: from Undruggable to Druggable?

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• The MYC oncogene is deregulated in approximately 70% of human cancers.
• Deregulated MYC drives tumorigenesis through intrinsic cellular mechanisms, tumor microenvironment modulation, and immune suppression.
• Targeting MYC is challenging due to its lack of a druggable pocket and nuclear localization.

Purpose of the Study:

• To review recent advancements in targeting the MYC oncogene for cancer therapy.
• To highlight novel anti-MYC compounds and their therapeutic potential.
• To discuss the implications of MYC inhibition on the tumor microenvironment and immunotherapy response.

Main Methods:

• Review of recent preclinical and clinical studies on anti-MYC agents.
• Analysis of the mechanisms of action for compounds like Omomyc and MYCi975.
• Evaluation of clinical trial data for MYC inhibitors.

Main Results:

• Development of novel anti-MYC compounds (Omomyc, MYCi975) with demonstrated anti-cancer activity in preclinical models.
• These compounds exhibit low short-term toxicity and enhance anti-tumor immune responses.
• Clinical trials, including a Phase I trial of OMO-103, indicate good tolerability and target engagement via decreased MYC-regulated gene expression.

Conclusions:

• Targeting MYC is a promising therapeutic strategy for a wide range of cancers.
• Emerging anti-MYC drugs show potential for monotherapy and combination with immunotherapy.
• Further clinical evaluation of MYC inhibitors is warranted.