Ignite Creation Date:
2024-05-06 @ 8:27 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06389201
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-29
First Post:
2024-04-25
Brief Title:
Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients
Sponsor:
Affiliated Hospital of Nantong University
Organization:
Affiliated Hospital of Nantong University
Study Overview
Official Title:
Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
Detailed Description:
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
Our 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
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
Our 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None