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 the investigators' attention because of their association with the clinical risk of nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous clinical data. In study, the investigators 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.

Although the majority of patients with nasopharyngeal carcinoma (NPC) do not present with overt metastases at diagnosis, a significant number succumb to disseminated disease years after the successful treatment of the primary tumor. Thus, late NPC recurrence may be the result of rare and elusive dormant cancer cells hiding in specialized niches being reactivated by specific signals. The concept of cancer dormancy has been described for the most common solid and hematological cancers; however, the dormant cancer cells in NPC remain largely uncharacterized.

Although many factors contribute toward cancer cell dormancy, recent studies have demonstrated that cancer therapy can induce cellular dormancy. Indeed, therapy-induced dormancy has been shown to lead to durable proliferation arrest, resulting in the formation of polyploid giant cancer cells (PGCCs), which are a unique sub-population of cancer cells that contribute toward the heterogeneity of solid tumors. Unlike regular-sized diploid cancer cells, PGCCs display distinct morphological features, including a large cytoplasmic area and a high genomic content contained within a single highly enlarged nucleus or multiple nuclei. Despite being present in low numbers, the frequency of PGCCs increases markedly after exposure to hypoxia and therapeutic interventions such as radiotherapy and chemotherapies.

The investigators' findings, which used a highly relevant clinical orthotopic model of imageable NPC and clinical data, suggest that autophagy inhibition (HCQ) prevents therapy-induced dormant PGCC formation and thereby prevents NPC metastasis.

Inclusion Criteria:

• Clinical diagnosis of NPC.
• Have not received any cancer therapies
• Must provide informed consent

Exclusion Criteria:

• With metastasis before the first treatment.

Study protocol, statistical analysis plan, informed consent form, clinical study report, and analytic code will be shared to other researchers.

Two years after this clinical trial finished.

Researchers must clearly state the purpose of their study and ensure it aligns with the scientific objectives of the data sharing initiative. A detailed research plan, including research design, data analysis methods, and expected results, should be provided to ensure the data is used in a reasonable and effective manner. Additionally, researchers must outline data security and privacy protection measures to ensure the safe storage, transmission, and use of the data in compliance with relevant regulations and policies.