Potential predictors of chemotherapy response in ovarian cancer—How do we define chemosensitivity?

2007 ◽  
Vol 104 (2) ◽  
pp. 345-351 ◽  
Author(s):  
S.A. O'Toole ◽  
B.L. Sheppard ◽  
A. Laios ◽  
J.J. O'Leary ◽  
E.P.J. McGuinness ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1420
Author(s):  
Sweta Sharma Saha ◽  
Lucy Gentles ◽  
Alice Bradbury ◽  
Dominik Brecht ◽  
Rebecca Robinson ◽  
...  

Defective DNA damage response (DDR) pathways are enabling characteristics of cancers that not only can be exploited to specifically target cancer cells but also can predict chemotherapy response. Defective Homologous Recombination Repair (HRR) function, e.g., due to BRCA1/2 loss, is a determinant of response to platinum agents and PARP inhibitors in ovarian cancers. Most chemotherapies function by either inducing DNA damage or impacting on its repair but are generally used in the clinic unselectively. The significance of HRR and other DDR pathways in determining response to several other chemotherapy drugs is not well understood. In this study, the genomic, transcriptomic and functional analysis of DDR pathways in a panel of 14 ovarian cancer cell lines identified that defects in DDR pathways could determine response to several chemotherapy drugs. Carboplatin, rucaparib, and topotecan sensitivity were associated with functional loss of HRR (validated in 10 patient-derived primary cultures) and mismatch repair. Two DDR gene expression clusters correlating with treatment response were identified, with PARP10 identified as a novel marker of platinum response, which was confirmed in The Cancer Genome Atlas (TCGA) ovarian cancer cohort. Reduced non-homologous end-joining function correlated with increased sensitivity to doxorubicin, while cells with high intrinsic oxidative stress showed sensitivity to gemcitabine. In this era of personalised medicine, molecular/functional characterisation of DDR pathways could guide chemotherapy choices in the clinic allowing specific targeting of ovarian cancers.


Author(s):  
Inna I. Antoneeva ◽  
Tatyana V. Abakumova ◽  
Dinara R. Dolgova ◽  
Tatyana P. Gening ◽  
Sabina S. Pirmamedova ◽  
...  

2016 ◽  
Vol 15 ◽  
pp. CIN.S40660 ◽  
Author(s):  
Alexandros Laios ◽  
Davide Volpi ◽  
Rajeev Kumar ◽  
Zoe Traill ◽  
Borivoj Vojnovic ◽  
...  

In patients with advanced ovarian cancer (AOC), additional imaging of disseminated disease at laparoscopy could complement conventional imaging for estimation of chemotherapy response. We developed an image segmentation method and evaluated its use in making accurate and objective measurements of peritoneal metastases in comparison to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. A software tool using a custom ImageJ macro-based approach was employed to estimate lesion size by converting image pixels into unit length. The software tool was tested as a proof-of-principle in an AOC patient with two isolated peritoneal deposits. Image analysis of representative laparoscopic snapshots before and after three cycles of neoadjuvant chemotherapy (NACT) revealed an average tumor nodule response ratio (TNRR) of 40% (partial response), which was in concordance with RECIST evaluation by computed tomography (CT). We demonstrated the feasibility of using this novel anatomical analysis for direct assessment of chemotherapy response in an AOC patient as an adjunct to RECIST criteria.


2016 ◽  
Vol 8 ◽  
pp. BIC.S35775 ◽  
Author(s):  
Urmila Sehrawat ◽  
Ruchika Pokhriyal ◽  
Ashish Kumar Gupta ◽  
Roopa Hariprasad ◽  
Mohd Imran Khan ◽  
...  

Conventional treatment for advanced ovarian cancer is an initial debulking surgery followed by chemotherapy combination of carboplatin and paclitaxel. Despite initial high response, three-fourths of these women experience disease recurrence with a dismal prognosis. Patients with advanced-stage ovarian cancer who underwent cytoreductive surgery were enrolled and tissue samples were collected. Post surgery, these patients were started on chemotherapy and followed up till the end of the cycle. Fluorescence-based differential in-gel expression coupled with mass spectrometric analysis was used for discovery phase of experiments, and real-time polymerase chain reaction, Western blotting, and pathway analysis were performed for expression and functional validation of differentially expressed proteins. While aldehyde reductase, hnRNP, cyclophilin A, heat shock protein-27, and actin are upregulated in responders, prohibitin, enoyl-coA hydratase, peroxiredoxin, and fibrin-β are upregulated in the nonresponders. The expressions of some of these proteins correlated with increased apoptotic activity in responders and decreased apoptotic activity in nonresponders. Therefore, the proteins qualify as potential biomarkers to predict chemotherapy response.


2019 ◽  
Vol 11 ◽  
pp. 1179299X1986081 ◽  
Author(s):  
Ruchika Pokhriyal ◽  
Roopa Hariprasad ◽  
Lalit Kumar ◽  
Gururao Hariprasad

Ovarian cancer is the seventh most common gynaecologic malignancy seen in women. Majority of the patients with ovarian cancer are diagnosed at the advanced stage making prognosis poor. The standard management of advanced ovarian cancer includes tumour debulking surgery followed by chemotherapy. Various types of chemotherapeutic regimens have been used to treat advanced ovarian cancer, but the most promising and the currently used standard first-line treatment is carboplatin and paclitaxel. Despite improved clinical response and survival to this combination of chemotherapy, numerous patients either undergo relapse or succumb to the disease as a result of chemotherapy resistance. To understand this phenomenon at a cellular level, various macromolecules such as DNA, messenger RNA and proteins have been developed as biomarkers for chemotherapy response. This review comprehensively summarizes the problem that pertains to chemotherapy resistance in advanced ovarian cancer and provides a good overview of the various biomarkers that have been developed in this field.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yong Jae Lee ◽  
Hyun-Soo Kim ◽  
John Hoon Rim ◽  
Jung-Yun Lee ◽  
Eun Ji Nam ◽  
...  

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