LDC4PCaTher · BMX-targeted ligand-drug conjugates for prostate cancer therapy
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-11-01 → 2019-01-12
- EU contribution
- €160,636
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
BMX-targeted ligand-drug conjugates for prostate cancer therapy
Cancer is the second leading cause of death worldwide with estimated 18.1 million new cases in 2018 that resulted in 9.6 million deaths, a number that is expected to grow within the next decades. One of the most frequently diagnosed types of cancer is Prostate Cancer (PCa), with 1.28 million cases reported worldwide in 2018. Despite the advances in chemotherapy, the risks associated with current therapies still carry severe side effects and offer limited benefit to the patients. These side effects arise from the fact that cytotoxic agents that should preferentially kill cancer cells and not healthy tissues often display poor targeting performances and accumulate in normal healthy cells as well as in tumours. As a consequence, the risks and side effects associated with current therapies range from erectile dysfunction, loss of fertility, and incontinence after surgery or even recurrence of an androgen-independent tumour after androgen-ablation therapy. The need for novel safe and effective treatments is therefore urgent. During this project, we aim to develop new ligand–drug conjugates (LDCs) that can efficiently target prostate cancer cells and delivered the cytotoxic payload in the tumour, killing the cancer cells and sparing the healthy ones.
Data: CORDIS, © European Union
Project objective
Standard of care strategies for the treatment of cancer still relies heavily on non-specific radiation and chemotherapy. These treatments are commonly associated with severe toxicities and in many cases only offer limited benefit for the patient. The targeted delivery of radionuclides, cytotoxic drugs and pro-inflammatory cytokines into malignant tissue, on the other hand, can markedly improve the therapeutic index and overall efficacy of such substances. Whilst monoclonal antibodies are the most widely used delivery vehicles to date, low molecular weight targeted agents are emerging as a promising alternative to antibody-based drug delivery. These ligands have negligible immunogenic risk and are easier to chemically modify enabling fine tuning of their ADME profile. As a result, it is possible to achieve a time dependent release of the cytotoxic payload at the target tissue maximizing its therapeutic efficacy while producing minimal damage to healthy cells. Most importantly, depth of tumour penetration and tumour-to-blood distribution ratio after injection should be significantly superior.We therefore propose to systematically investigate the targeting performance of bone marrow tyrosine kinase in chromosome X (BMX) ligands for the targeted delivery of cytotoxic drugs into BMX-overexpressing tumours, namely prostate cancer. This project aims at (1) demonstrate that a BMX ligand can selectively accumulate in BMX-overexpressing cancers; (2) developing a general chemical approach for building safe ligand-drug conjugates (LDCs); and (3) when site-specifically conjugated to cytotoxic drug, this novel LDC is highly effective for the treatment of prostate cancer. This project is expected to explore new avenues for drug delivery systems since the concepts here proposed go beyond prostate cancer therapy as they can be applicable to any ligand that interferes with up-regulated disease-related pathways.
Original text from CORDIS.
Participants
- INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES · LisboaCoordinatorPortugal
Links
Data: CORDIS, © European Union