Circulating Cell-Free DNA as Biomarker of Taxane Resistance in Metastatic Castration-Resistant Prostate Cancer

• Published in: Cancers Vol. 13; no. 16; p. 4055
• Main Authors: Francini, Edoardo, Ou, Fang-Shu, Rhoades, Justin, Wolfe, Eric G., O’Connor, Edward P., Ha, Gavin, Gydush, Gregory, Kelleher, Kaitlin M., Bhatt, Rupal S., Balk, Steven P., Sweeney, Christopher J., Adalsteinsson, Viktor A., Taplin, Mary-Ellen, Choudhury, Atish D.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 12.08.2021; MDPI
• Subjects: Biomarkers; Cancer therapies; Castration; cell-free DNA; Chemotherapy; Computer applications; Copy number; Deoxyribonucleic acid; DNA; DNA sequencing; Gene amplification; Genomes; Invasiveness; Metastases; Metastasis; metastatic castration-resistant prostate cancer; Ovaries; Patients; Plasma; Prostate cancer; Statistical analysis; Taxanes; Whole genome sequencing; United States > US
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13164055

There are no biomarkers predictive of resistance to docetaxel or cabazitaxel validated for patients with metastatic castration-resistant prostate cancer (mCRPC). We assessed the association between ABCB1 amplification and primary resistance to docetaxel or cabazitaxel for patients with mCRPC, using circulating cell-free DNA (cfDNA). Patients with ≥1 plasma sample drawn within 12 months before starting docetaxel (cohort A) or cabazitaxel (cohort B) for mCRPC were identified from the Dana–Farber Cancer Institute IRB approved database. Sparse whole genome sequencing was performed on the selected cfDNA samples and tumor fractions were estimated using the computational tool ichorCNA. We evaluated the association between ABCB1 amplification or other copy number alterations and primary resistance to docetaxel or cabazitaxel. Of the selected 176 patients, 45 samples in cohort A and 21 samples in cohort B had sufficient tumor content. No significant association was found between ABCB1 amplification and primary resistance to docetaxel (p = 0.58; odds ratio (OR) = 1.49) or cabazitaxel (p = 0.97; OR = 1.06). No significant association was found between exploratory biomarkers and primary resistance to docetaxel or cabazitaxel. In this study, ABCB1 amplification did not predict primary resistance to docetaxel or cabazitaxel for mCRPC. Future studies including ABCB1 amplification in a suite of putative biomarkers and a larger cohort may aid in drawing definitive conclusions.