Introduction

New therapeutic approaches for cancer treatment are needed to overcome the lack of efficacy and selectivity of current approaches, as well as their significant side effects. This patent protects peptides with anticancer activity capable of targeting the enzyme hexokinase 2 (HK2) in different types of tumors.

Technical features

HK2 is a glycolytic enzyme that contributes to the metabolism, growth and death inhibition of tumor cells. Its expression is associated with poor prognosis and chemotherapeutic/radiation resistance in various solid and hematopoietic tumors. The peptides identified in this patent belong to Activatable Cell Penetrating Peptides (ACPPs) family, designed to selectively target the HK2 in tumors maximizing their efficacy while limiting off-target side effects in healthy tissues. This process induces tumor cell death in minutes by activating the apoptotic cell-death pathway. Cell death through apoptosis leads to rapid and selective clearing of tumor cells without eliciting inflammation, and avoiding potential toxic effects caused by the inflammatory process.

Preclinical in-vivo experimentation is ongoing; the lead peptide halts tumor growth in preclinical mouse models of breast and colon cancer, and Malignant Peripheral Nerve Sheath Tumor (MPNST), with a success rate close to 100%.

Possible Applications

• Selective targeting of tumor cells;
• Activation of apoptotic tumor cell death;
• Limited off-target side effects in healthy tissues;
• Reduced toxicity.

Advantages

• Treatment of benign and malignant tumors expressing HK2;
• Treatment of solid and hematopoietic tumors expressing HK2;
• Treatment of metastatic tumors expressing HK2;
• Treatment of drug/radiation resistant tumors that over-express HK2.