Precision medicine by designer interference peptides: applications in oncology and molecular therapeutics

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• Many key cancer-driving proteins (oncogenic drivers) are undruggable by traditional small molecules or biologics due to their structure and cellular location.
• Proteins like MYC and KRAS are crucial in cancer but lack druggable pockets and are inaccessible to large molecules.
• Current cancer therapeutics can only target a small fraction of known cancer gene products.

Purpose of the Study:

• To review recent advances in using designer interference peptides (iPeps) to inhibit challenging cancer oncoproteins.
• To discuss the development of multimodal peptides designed to overcome the limitations of earlier iPep generations.
• To highlight the potential of iPeps as programmable tools for precision cancer medicine.

Main Methods:

• Review of current literature on interference peptides (iPeps) for targeting oncogenic drivers.
• Discussion of strategies to enhance iPep efficacy, including multimodal peptide development.
• Analysis of cell-type specificity of protein-protein interactions for targeted therapy.

Main Results:

• Interference peptides (iPeps) have shown success in inhibiting multiple oncogenic drivers, with some progressing to clinical trials.
• Multimodal peptide designs are being developed to address limitations such as intracellular delivery, tissue specificity, and potency.
• Advances enable selective manipulation of the cancer cell oncoproteome.

Conclusions:

• Interference peptides (iPeps) represent a viable strategy for targeting previously undruggable cancer proteins.
• Multimodal peptide development is crucial for overcoming the clinical translation barriers of iPeps.
• Programmable iPep approaches hold significant promise for developing novel precision medicine tools in cancer treatment.