Liquid biopsy to monitor early relapse of gynaecological malignancies

Liquid biopsy is the collection of circulating tumor cells (CTCs) and/or circulating tumor DNA (ctDNA) from non-solid biological tissue, primarily blood, for clinical purposes. In conjunction with next-generation sequencing, liquid biopsy is a non-invasive and rapid procedure, easily repeatable and highly sensitive, all advantages that make it an ideal tool to monitor the course of gynaecological malignancies, previously diagnosed on solid biopsy or surgical specimen. In the form of a blood draw, it may be performed at various time points throughout the treatment regimen to evaluate the appearance of resistant gene mutations, and also revealing the tumor’s mutational burden and microsatellite instability status. Moreover, it can track minimal residual disease and predict tumor recurrence months or years before conventional imaging methods, allowing an early detection of cancer relapse and offering support to targeted therapy.

Liquid biopsy; Fluid biopsy; Circulating tumor cell (CTC); Circulating tumor DNA (ctDNA); Next-generation sequencing (NGS); Cancer.

[1] Crowley E., Di Nicolantonio F., Loupakis F., Bardelli A.: “Liquid biopsy: monitoring cancer-genetics in the blood”. Nat. Rev. Clin. Oncol., 2014, 10, 472-484.

[2] Aseworth T.R.: “A case of cancer in which cells similar to those in the tumours were seen in the blood after death”. Aust. Med. J., 1869, 14, 146-147.

[3] Gupta G. P., Massagué J.: “Cancer metastasis: building a framework”. Cell, 2006, 127, 679-695.

[4] Schwarzenbach H., Hoon D.S.B., Pantel K.: “Cell-free nucleic acids as biomarkers in cancer patients”. Nat. Rev. Cancer, 2011, 11, 426-437.

[5] Heitzer E., Ulz P., Geigl J.B.: “Circulating tumor DNA as a liquid biopsy for cancer”. Clin. Chem., 2015, 61, 112-123.

[6] Clark T.A., Chung J.H., Kennedy M., Hughes J.D., Chennagiri N., Lieber D.S., et al.: “Analytical validation of a hybrid capture-based next-generation sequencing clinical assay for genomic profiling of cell-free circulating tumor DNA”. J. Mol. Diagn., 2019, 20, 686-702.

[7] Roncati L., Vadalà M., Valentina P., Corazzari V., Palmieri B.: “Genomic profiling in gynaecological oncology: the future is now!”. Eur. J. Gynaecol. Oncol., 2020, 41, 323-325.

[8] Roncati L., Barbolini G., Sartori G., Siopis E., Pusiol T., Maiorana A.: “Loss of CDKN2A promoter methylation coincides with the epigenetic transdifferentiation of uterine myosarcomatous cells”. Int. J. Gynecol. Pathol., 2016, 35, 309-315.

[9] Roncati L., Manenti A., Pusiol T., Piscioli F., Barbolini G., Maiorana A.: “Testosterone aromatization to estradiol in course of ovarian functioning brenner tumor associated with endometrial carcinoma and endometriosis (Roncati-Manenti Triad)”. J. Gynecol. Oncol., 2016, 26, 1461-1464.

[10] Wang Y., Shi C., Eisenberg R., Vnencak-Jones C.L.: “Differences in microsatellite instability profiles between endometrioid and colorectal cancers”. J. Mol. Diagn., 2017, 19, 57-64.

[11] Roncati L.: “Microsatellite Instability predicts response to anti-PD1 immunotherapy in metastatic melanoma”. Acta Dermatovenerol. Croat., 2019, 26, 341-343.

[12] Olsson E., Winter C., George A., Chen Y., Howlin J., Tang M. E., et al.: “Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease”. Embo. Mol. Med., 2016, 7, 1034-1047.

[13] European Medicines Agency. Lynparza (olaparib). An overview of Lynparza and why it is authorised in the EU. Amsterdam, Netherlands: European Medicines Agency; 2019 [accessed 2019 June]. Available at: https://www.ema.europa.eu/en/documents/overview/lynparza-epar-medicine-overview_en.pdf.

[14] U.S. Food & Drug Administration. FDA approves rucaparib for maintenance treatment of recurrent ovarian, fallopian tube, or primary peritoneal cancer. Silver Spring, MD: U.S. Food & Drug Administration; 2018 [accessed 2018 April 4]. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rucaparib-maintenance-treatment-recurrent-ovarian-fallopian-tube-or-primary-peritoneal.

[15] U.S. Food & Drug Administration. FDA approves niraparib for HRD-positive advanced ovarian cancer. Silver Spring, MD: U.S. Food & Drug Administration; 2019 [accessed 2019 October 23]. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-hrd-positive-advanced-ovarian-cancer.

[16] Roncati L., Pusiol T., Piscioli F., Barbolini G., Maiorana A., Lavezzi A.: “The first 5-year-long survey on intrauterine unexplained sudden deaths from the Northeast Italy”. Fetal. Pediatr. Pathol., 2016, 35, 315-326.

[17] Roncati L., Piscioli F., Pusiol T.: “The endocrine disrupting chemicals as possible stillbirth contributors”. Am. J. Obstet. Gynecol., 2016, 215, 532-533.

[18] Roncati L., Pusiol T., Piscioli F., Lavezzi A.M.: “Neu-rodevelopmental disorders and pesticide exposure: the northeastern Italian experience”. Arch. Toxicol., 2017, 91, 603- 604.