HCR.20.006 – Targeting tumor stroma to enhance therapeutic efficacy in difficult-to-treat cancers

Route: Health care research, sickness prevention and treatment

Cluster question: 098 How can we use breakthroughs in basic biomedical research to develop new medicines?

Difficult-to-treat cancers such as pancreatic, oesophageal and gastric tumors have seen hardly any significant benefit in the patient survival in the last 30 years, despite enormous improvements in the technologies for diagnosis and treatment of cancers. Patients and their families live under high uncertainty and have a dismal quality of life. Nanomedicines have been developed to improve the efficacy of chemotherapy and reduce adverse effects. However, they also remain ineffective in these cancer types. A major reason for this lack of response lies in the presence of dense tumor stroma which shelter cancer cells and prevent the penetration of anti-cancer agents/nanomedicine to kill cancer cells. There is an urgent unmet clinical need to develop novel technologies to inhibit tumor stroma to combat these difficult-to-treat cancers. In this project, we propose to develop tumor stroma-modulating technologies able to disrupt stroma barrier by inhibiting the matrix production and thereby enhance the penetration of nanomedicine. We propose to create a specialized interdisciplinary team including experts from material science, nanotechnology, applied bioengineering, pharmaceutical- and biomedical sciences to realize an impactful strategy. Advanced drug delivery systems will be developed containing novel anti-stromal peptides and nanomedicine for example, for systemic treatment, targeted nanoparticles and for local treatment, hydrogels will be developed. Advanced tumor-on-a-chip models mimicking tumor stroma will be developed for optimal and a high throughput testing of the technology. To realize the goal of personalized medicine, we will set up in vivo radioimaging of labeled stroma-targeting peptides to detect the tumor stroma content and heterogeneity. The therapeutic efficacy of the formulations will be examined in vivo in clinically-relevant stroma-rich tumor models to study the impact on stroma alteration, tumor growth, metastasis formation and survival. We will advance the best performing technology for its clinical

Keywords

cancer therapy, drug delivery, Nanomedicine, Tumor stroma

Other organisations

Leiden Universitair Medisch Centrum (LUMC), Utrecht University (UU)

Submitter

Organisation University of Twente (UT)
Name Prof.dr. J. (Jai) Prakash
E-mail j.prakash@utwente.nl
Website https://www.utwente.nl/en/tnw/bst/people/scientific/prakash/