Nanomedicine has emerged as a potential therapy for pancreatic cancer, a disease with a 5-year survival rate as low as 5%. The international project NoCanTher was launched in 2016 to test the use of magnetic nanoparticles in treating locally advanced pancreatic cancer. NoCanTher enters its final phase with the start-up of a clinical study led by the Vall d'Hebron Institute of Oncology (VHIO).
This project is aimed at patients with unresectable, locally advanced pancreatic cancer that has not metastasized, who have palliative chemotherapy as the only therapeutic alternative. Novel approaches are therefore required to increase the efficacy of chemotherapy. This population accounts for 20% of patients with pancreatic cancer.
The recently launched clinical study is based on the results obtained from the preclinical stage of NoCanTher, involving the CIBBIM-Nanomedicine Drug Delivery and Targeting Group, led by Simón Schwartz Jr. that assumed a key role in this first phase. This research focused on the development of iron magnetic nanoparticles that generate magnetic hyperthermia, where the heat generated can be used to sensitize cancer cells to the standard of care, and even destroy them directly.
VHIR and the Hospital of Fuenlabrada, Madrid, assessed the utility of nanoparticles in animal models in which pancreatic cancer was either induced or patient-derived tumors were implanted. The study demonstrated that the hyperthermia generated when nanoparticles are injected directly into the tumor both reduces the volume of the tumor and induces physical changes that favor the impact of chemotherapy against cancer cells. "This demonstrates a significant synergy between the hyperthermia generated by the nanoparticles and chemotherapy for pancreatic cancer", explains Simón Schwartz Jr, director of the VHIR CIBBIM-Nanomedicine Group.
These nanoparticles are heated after the application of an alternateing magnetic field and boost the effects of concurrently-administered chemotherapy; the gold standard therapy for these patients. "We think that, with this novel technique, we can change the characteristics of the tumor and control the disease locally. This pilot study represents an important step forward in opening up new therapeutic avenue for patients with locally advanced pancreatic cancer, for whom there are no other alternatives but chemotherapy", says Teresa Macarulla, Medical Oncologist at the Vall d’Hebron University Hospital, and Principal Investigator of VHIO’s Gastrointestinal and Endocrine Tumors Group ), who leads NoCanTher’s clinical study.
In parallel, VHIR and VHIO will take blood samples from patients to determine whether this therapy reduces the number of circulating tumor cells in blood, especially tumor stem cells, which can generate new tumor cells and metastasize. The project also involves a cutting-edge radiomic analysis technique.
In collaboration with other partners, the Academic Research Organization (ARO) of the VHIR, is participating in the implementation and follow-up of the clinical trial, which will evaluate the feasibility of this new therapy.
The local heat induced by nanoparticles increases the efficacy of chemotherapy.
Our approach based on magnetic iron oxide nanoparticles makes it possible to apply heat solely in the region where these nanoparticles are present, in this case, the pancreatic tumor. By this technique, chemotherapy does not damage the healthy tissue surrounding the tumor. Hyperthermia transforms electromagnetic energy into heat, which, combined with standard chemotherapy, destroys tumor cells and controls the local growth of the tumor. A magnetic field generator (NTT Generator) specifically designed and built to generate thermal energy inside the tumor will be used in this study.
Although this is a relatively new field of research, this approach may be a feasible option for cancer patients, especially for those who do not respond to standard treatment and in whom external beam radiotherapy can cause high toxicity.
A long-haul multidisciplinary project that ends with a clinical study.
Under the coordination of IMDEA Nanociencia, eleven national and international research centers are members of the NoCanTher – Nanomedicine upscaling for early clinical phases of multimodal cancer therapy – Consortium: BioKeralty Research Institute (Miñano, Spain), ImmuPharma (London, England), Chemicell (Berlin, Germany), University Hospital (Jena, Germany), Resonant Circuits (London, England), Vall d’Hebron Research Institute (VHIR) (Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain), Trinity College (Dublin, Ireland), Université Paris Diderot (Paris, France),
Vall d’Hebron Institute of Oncology (VHIO) (Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain), Hospital Universitario de Fuenlabrada (Madrid, Spain).
This initiative is funded under the Horizon 2020 programme (GA: 685795).