Speaker
Description
Radiation-induced lung injury, characterized by chronic inflammation and fibrosis, limits the dose we can give in lung cancer radiotherapy. Drugs that block the inflammatory/fibrosis response have been shown to protect normal lung tissues from radiation. In this study, we wish to determine if one of these drugs also protect the lung cancer cells.
To initiate this study, we developed and validated a protocol to irradiate cell cultures in 12 well plates with an orthovoltage x-ray unit. This is followed by employing clonogenic survival assays to assess the effects of a drug that blocks fibrosis response in a non-small cell lung cancer (NSCLC) cell line A549. Specifically, the drug we employed is a novel compound (peptide) that blocks cells’ RHAMM (Receptors for Hyaluronan Mediated Motility) receptors from being activated.
Dosimetric accuracy of the irradiation setup was verified using GAFchromic films after calibration. Cell survival was quantified using clonogenic assays after optimization of seeding density across preliminary trials. We obtained the radiation cell survival curve by radiating between 2-10 Gy in 2 Gy increments. NSCLC cells were then pre-treated with peptide concentrations of 0.5, 5, and 50 μM prior to 4 Gy irradiation. Sensitizer enhancement ratios (SER) and statistical significance were calculated.
The GAF film exponential curve fit had an R^2 value of 0.996 and a mean difference of 3.1% in a test trial. Dose profiles underneath the wells had a 95.6% flatness and a mean difference of 5.5%. Across two independent peptide trials, no statistically significant difference between peptide-treated and control was observed. At 4 Gy, SER values for the three concentrations were 1.17 (0.5 μM, p=0.68), 1.15 (5.0 μM, p=0.72), and 1.18 (50.0 μM, p=0.60).
Preliminary results indicate that peptide pre-treatment did not alter radiation response under the test conditions. Ongoing work includes adding the peptide after the radiation, radiating at higher doses, and better modelling the tumour microenvironment using spheroids.
This study assessed a novel anti-fibrosis drug for use in lung cancer cells. We integrated biological assays with physics dosimetry to provide foundational data to increase therapeutic ratios for lung radiotherapy.
| Keyword-1 | Non–small cell lung cancer |
|---|---|
| Keyword-2 | Radiation dosimetry |
| Keyword-3 | Sensitizer enhancement ratio |