A higher frequency of [Ca2+]i spikes were found in PBMCs cultured in BxPC3-SMAD4+, but mainly in BxPC3 complete CM, and these variation were reproduced by Exo enriched media, suggesting that in case of SMAD4 loss cancer derived Exo magnify their ability to induce an increased calcium trafficking in PBMCs. The gene discussed is SMAD4; the disease is cancer.