Poor prognosis outcome tumors, bacteria-infected tumors and nanodrugs: current evidence and hypotheses towards a paradigm change for treatment

Abstract

New therapies and supportive care have converted several cancer types into chronic conditions. Yet, some tumors exhibit features reproducibly correlated with poor prognosis outcome (PPO-tumors). Bacteria in a tumor environment can inactivate chemotherapeutics and are a feature of PPO-tumors, although standard diagnostic tests for tumor infections do not exist. Optimism is high for nanotechnologic innovations but nanoparticulate chemotherapeutics based on enhanced permeability and retention in a human tumor environment have only shown limited treatment benefits. Moreover, treatment of infected tumors in animals with stimuli-responsive nanocarriers loaded with an antibiotic/chemotherapeutic combination has demonstrated limited benefits compared to treatment with combinations of carrier-free antibiotics and chemotherapeutics. Development of nanoparticulate chemotherapeutics with significant benefits in human clinical use is estimated to take several decades, which is too long for patients with PPO-tumors. Herein we hypothesize the following: 1-all diagnosed PPO-tumors are infected with bacteria; 2-all PPO-tumors in mice and humans exhibit enhanced permeability to chemotherapeutics; and 3-all diagnosed PPO-tumors must be treated from the onset with a combination of carrier-free antibiotics and chemotherapeutics. Each hypothesis was critically evaluated and judged plausible and clinically acceptable. Potential clinical treatment of PPO-tumors, presuming bacterial infection without diagnosis, with an approved antibiotic and chemotherapeutic free drug combination requires a paradigm change in treatment concept towards more lenient antibiotic use. However, many cancer patients already require antibiotics during chemotherapeutic treatment and combined carrier-free antibiotic/chemotherapeutic treatment may provide an immediate pathway to re-sensitize PPO-tumors to clinically used chemotherapeutics and alter the prognosis to a more favourable outcome.