Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients

Recurrence and metastasis

Dormant cancer cells that survive anti-cancer therapy can lead to cancer recurrence and
 disseminated metastases that prove fatal in most cases. Recently, specific dormant polyploid
 giant cancer cells (PGCC) have drawn our attention because of their association with the
 clinical risk of nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous
 clinical data. In study, we report the biological properties of PGCC, and reveal that
 autophagy is a critical mechanism of PGCC induction. Moreover, pharmacological inhibition of
 autophagy greatly impaired PGCC formation, significantly suppressing metastasis and improving
 survival in a mouse model. Mechanistically, chemotherapeutic drugs partly damaged
 mitochondria, and activated autophagy to promote PGCC formation. High numbers of PGCCs
 correlated with shorter recurrence time and worse survival outcomes in NPC patients.
 Collectively, these findings suggest a therapeutic approach of targeting dormant PGCCs in
 cancer.
 
 Pretreatment with an autophagy inhibitor (HCQ) before chemotherapy and radiotherapy could
 prevent formation of therapy-induced dormant polyploid giant cancer cells, thereby reducing
 recurrence and metastasis of nasopharyngeal carcinoma.