Abstract 39P
Background
Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells, but repressed in human somatic cells. It was recently identified as a potential target for anti-cancer immunotherapy. Exosomes are nano-sized particles secreted from all types of cells, containing a molecular cargo that reflects their cells of origin. Exosomal hTERT mRNA can be detected in the serum of patients with solid malignancies, but not in healthy individuals. We sought to evaluate the feasibility of measuring serum exosomal hTERT transcripts levels in patients with lung cancer at diagnosis and during the course of their disease.
Methods
A prospective collection of hTERT mRNA levels in serum-derived exosomes from patients (pts) with stage III-IV lung cancer (SCLC & NSCLC). hTERT level above 1.2 was considered "detectable” according to a previous ROC curve. Demographic and clinical data were collected retrospectively from patient charts. Overall response to systemic therapy (chemotherapy, immunotherapy and tyrosine kinase inhibitors) was evaluated by the treating physicians.
Results
Serum was collected from 51 pts (47 – NSCLC, 4-SCLC). Sequential measurments were obtained in 71% of pts (36/51). hTERT was detected in 51% (26/51) of pts with lung cancer. Mean hTERT levels were 4.03±0.86 in all 21 pts with detectable hTERT at 1st measurment. Changes in exosomal hTERT mRNA levels reflected the clinical course of most patients. Among pts with partial response, 82% (nine out of 11) exhibited concomittant decrease, while 18% demonstarted increase in exosomal hTERT levels. Among pts with progressive disease, 50% (four out of eight) had elevated exosomal hTERT levels correlating with the disease progression, and 50% exhibited a decrease.
Conclusions
Exosomal hTERT mRNA levels are elevated in 51% of patients with lung cancer. These preliminary data suggest a potential association between hTERT levels and response to therapy. The cohort is being expanded to assess correlation between exosomal hTERT levels and efficacy of immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Cancer - Davidoff Center.
Funding
Cancer - Davidoff Center.
Disclosure
All authors have declared no conflicts of interest.