Optimizing delivery and effectiveness of chemotherapy in breast cancer patients using thermotherapy under image-guidance

ended

With 1.67 million of diagnoses and 522,000 deaths in 2012, breast cancer is the most common and the leading cause of cancer death among women worldwide. Most patients with breast cancer undergo chemotherapy before or after surgery. Chemotherapy is generally applied as a systemic therapy, with only less than 1% of the administered drugs actually reach the tumour. This causes severe side-effects in normal tissue, and often prevents the administration of sufficient dose for effective cure. Thermotherapy, also known as hyperthermia, that is the increase of tumour temperature to 40-43°C, improves drug delivery at the tumour area and amplifies the anti-tumour effect of the drugs (biological and spatial selectivity). Despite this two-fold potential, thermo-chemotherapy is currently not used in breast cancer due to the inability to heat only the tumour area. Thermotherapy improves perfusion, extravasation and membrane fluidity in the heated region, leading to an increased bioavailability and drug concentration. Furthermore, heating above 41°C inhibits DNA double strand break damage repair and induces an anti-cancer immune response. As for the future potential of thermotherapy, it will be the key for the groundbreaking technology of thermosensitive smart nano-carriers, enabling a focalized delivery of chemotherapy load. Exploiting the full potential of my envisaged approach of improving clinical outcomes for primary breast cancer requires a precise application of thermotherapy. Unfortunately, current state-of-the-art commercial and experimental solutions do not conform to the intact breast, cannot selectively treat deep-seated tumours near the chest wall nor provide the 3D heat steering capabilities to specifically heat large tumour volumes. Therefore I propose this project with the main research goal to develop a novel, MR compatible thermotherapy system for MR-adaptive spatial and biological chemo-targeting in primary breast cancers.