Advanced Engineering of Nitric Oxide Based Therapeutics for Triple Negative Breast Cancer Training Network

NO-CANCER-NET will focus on Triple Negative Breast Cancer (TNBC) and Nitric Oxide (NO)-related therapeutic development. TNBC accounts for 10-20% breast cancers and is characterised by diagnosis at an early age and an aggressive phenotype. It indeed develops incurable distant metastasis within the first 2-3 years in approximately 30% patients. Despite significant efforts, TNBC treatment is limited to surgery and chemotherapy laying bare the urgent need for new targeted therapeutic development. Our network has demonstrated an important role for inducible nitric oxide synthase (iNOS) and NO signalling in TNBC metastatic progression, with efficacy of iNOS targeting demonstrated in a phase I/II clinical trial of patients with distant metastasis. Based on NO’s yin/yang effect on tumour biology, iNOS/NO system can be targeted by either inhibiting iNOS and reducing the physiological levels of NO which drive tumour progression, or vice versa using NO donating drugs to increase NO to tumouricidal levels (similar to immune cells NO-mediated tumour targeting).

The NO-CANCER-NET Doctoral Network (DN) addresses two fundamental gaps in European training: 1) a network where a core of Doctoral Candidates (DCs) can share a basic understanding of molecular target discovery, models of tumour biology assessment, drug synthesis and delivery, developing diagnostics, handling complex spatial imaging and omics expression data profiles; and 2) solid interdisciplinary training in experimental, computational and clinical research. NO-CANCER-NET will equip our DCs to understand the complexities of bench to bedside cancer research, the importance of an interdisciplinary approach and an understanding of the fundamentals of related disciplines. This will be of great importance in preparing DCs to work between academia, industry and in clinical healthcare providers.