Efficacy of ChemoID® guided drug selection for palliative chemotherapy in advanced recurrent high-grade ovarian adenocarcinoma: Case study

Abstract

Notwithstanding tremendous advances in surgery, primary chemotherapy, and novel treatments for recurrent disease, the diagnosis of advanced epithelial ovarian cancer (EOC) in 2016 remains ultimately fatal in the majority of cases. Advanced therapy refractory EOC patients are often treated in hospice and with chemotherapy palliative care. The main goals of chemotherapy for recurrent/refractory ovarian cancer are the palliation of disease-related symptoms, and improvement of quality and quantity of life. Unfortunately, there is contradicting evidence suggesting that chemotherapy has a role in palliation of symptoms with an apparent improvement in quality of life. Anticancer drugs have a high rate of failure and chemotherapy response assays have been used to identify which drugs are more likely to be effective against those of gynecological origin. ChemoID® is a functional drug response assay which measures the sensitivity of cancer stem cells (CSCs) and bulk of tumor cells to chemotherapy to determine the most effective combination of anticancer drugs for solid tumors. We present a clinical case that demonstrates the utility of ChemoID® guidance to commonly available drugs with identified toxicity profiles and predictable cost profile available at POS, along with rapid response in correcting symptomatic disease features, and minimal treatment burden from toxicities. We observed in the reported case the survival and symptom management benefits of ChemoID® guided therapy even after plateau of response to cisplatin. Further studies are indicated to increase the clinical adoption of ChemoID® for gynecological malignancies in the palliative setting.

Clinical relevance of cancer stem cell chemotherapeutic assay for recurrent ovarian cancer

“…Details regarding the CSCs cytotoxicity assay (ChemoID) procedure have been described elsewhere [ [27] , [28] , [29] , [30] , [31] , [32] , [33] ]. In brief, primary cancer cell cultures were initiated from malignant cells present in the ascites or pleural aspirates.…”

“…In brief, primary cancer cell cultures were initiated from malignant cells present in the ascites or pleural aspirates. CSCs were enriched from the primary cancer cell cultures (bulk of tumor cells) as described previously [ [27] , [28] , [29] , [30] , [31] , [32] , [33] ] using a novel cell culture bioreactor with a membrane that allows for gas exchange. Cells were counted and a range of 1 × 10 6 –1 × 10 7 cells were cultured for 7–10 days.…”

“…The cells were challenged for a 1-h pulse with the panel of anticancer drugs ( Table 1 ). MTT assay was performed 48-h following chemotherapy treatment to assess cell survival as previously described [ 27 , 28 , 30 , [32] , [33] , [34] ]. Inhibition of bulk of tumor cells and CSCs survival was measured for each concentration (average counts in five replicates ± SE) of a given treatment (15–18 different treatments per patient).…”