Researchers target metastases

In several mouse models of cancer the team headed by Guido Serini and Enrico Giraudo at Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) showed that their vessel repair approach worked: an engineered version of the nerve growth factor and angiogenesis semaphorin-3A boosted the sensivity of tumour cells against chemotherapy. The scientists believe that their protein drug can be utilised as both a stand-alone treatment and as an addition to established anticancer therapies.

Blood vessels in tumours have an abnormal structure  leading to a reduced blood flow and oxygen supply, which can hamper cancer drug delivery and promote metastases. Growing evidence suggests that correction of  the vessel structure improves both oxygenation and blood flow restoring the efficacy of standard cancer therapies.

Initial clinical studies with the new angiogenesis blocker semaphorin-3A, however, caused serious adverse effects by the protein's interaction with the NRP1 receptor. Genetic engineering of the SEMA3A gene delivered a mutated protein that does no longer interact with the NRP1 pathway. The compound suppressed tumour growth, reduced metastasis and prolonged survival in mouse models of the most deadly human tumour type: pancreatic cancer.

The engineered semaphorin3A protein also enhanced tumour-suppressive effects of the chemotherapeutic gemcitabine,. The authors call for further assessment of their drug candidate's activity against other cancer types, but say that the compound could potentially find use as a therapy for cancers and other diseases that impact blood vessel formation. 

Previous publications have attributed both, cancer-blocking and tumour-promoting effects to semaphorin-3A.