Daniele Lo Re

University of Granada, Spain

Title: Peptide?Platinum(IV) conjugation minimizes the negative effect of chemotherapy on the tumour microenvironment

---

Biography

Dr. Daniele Lo Re he is Professor of University of Granada, Spain.

Abstract

Platinum analogues stand among the most universally utilized anti-cancer agents. Yet, the relative success of Pt-based therapies comes at the cost of severe, dose-limiting side effects due to their systemic cytotoxicity against non-malignant cells. A substantial proportion of colorectal cancer (CRC) patients does not benefit from standard oxaliplatin based-chemotherapy and almost 50% of them will develop metastases due to the emergence of resistance to treatment. It has been demonstrated that the tumor microenvironment retains high levels of oxaliplatin long time after therapy and oxaliplatin induce a pro-oncogenic program in the tumor stroma that associates with reduced survival of CRC patients. Here, we report the synthesis of a novel Pt(IV) analogue coupled to a cell-penetrating peptide (C-POC) designed for the treatment of colorectal cancer. Biological evaluation using patient-derived primary tumor organoids in vitro and in vivo indicates that C-POC displays a robust anti-cancer efficacy and a reduced capacity to accumulate in healthy organs compared to standard Pt-based therapy. In addition, C-POC uptake in non-malignant cells from the tumor microenvironment remains limited, leading to a lowered accumulation of versican (VCAN), a poor prognosis biomarker upregulated in patients treated with standard platinum therapy. In the era of personalized medicine, the conversion of a systemic drug into a targeted therapy, illustrated by the C-POC analogue, could set the stage for new strategies considering the impact of anti-cancer treatment on non-cancerous cells.