Role of antibodies in diagnosis and treatment of ovarian cancer: Basic approach and clinical status

Bhatt, Priyanka; Vhora, Imran; Patil, Sushilkumar; Amrutiya, Jitendra; Bhattacharya, Chandrali; Misra, Ambikanandan; Mashru, Rajashree

doi:10.1016/j.jconrel.2016.02.008

Cited by 52 publications

(23 citation statements)

References 146 publications

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“…Oncoscint® (B72.3 antibody conjugated to indium-111) was approved by FDA as a diagnostic in 1992 36 for whole body imaging for recurrences of ovarian and colorectal cancers. While Oncoscint® was found to be safe and effective in detecting tumors, this product was eventually discontinued due to PET (positron emission tomography) technology advancements in detecting metastatic lesions 37 . The regulatory approval and strong safety profile of Oncoscint® 38 led to the development of the second generation TAG-72 murine antibody CC49, which was evaluated for efficacy in Phase 2 clinical trials 39 .…”

Section: Discussionmentioning

confidence: 99%

Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity

Prendergast

Silva

Eavarone

et al. 2017

mAbs

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Targeted therapeutics that can differentiate between normal and malignant tumor cells represent the ideal standard for the development of a successful anti-cancer strategy. The Sialyl-Thomsen-nouveau antigen (STn or Sialyl-Tn, also known as CD175s) is rarely seen in normal adult tissues, but it is abundantly expressed in many types of human epithelial cancers. We have identified novel antibodies that specifically target with high affinity the STn glycan independent of its carrier protein, affording the potential to recognize a wider array of cancer-specific sialylated proteins. A panel of murine monoclonal anti-STn therapeutic antibodies were generated and their binding specificity and efficacy were characterized in vitro and in in vivo murine cancer models. A subset of these antibodies were conjugated to monomethyl auristatin E (MMAE) to generate antibody-drug conjugates (ADCs). These ADCs demonstrated in vitro efficacy in STn-expressing cell lines and significant tumor growth inhibition in STn-expressing tumor xenograft cancer models with no evidence of overt toxicity.

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Section: Discussionmentioning

confidence: 99%

Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity

Prendergast

Silva

Eavarone

et al. 2017

mAbs

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“…Besides, among all ovarian cancers, epithelial ovarian cancer (EOC) accounts for 80-90% (4), and has the highest mortality rate of all gynecological malignancies. Regardless of advances in treatment techniques, long-term survival rates for patients remain poor (2), maybe because of the lack of early symptoms, late diagnosis and invalid chemotherapy (5). Therefore, to ameliorate poor survival outcomes, obtaining earlier diagnosis and new prognostic indicators is critical.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of ARF1 is associated with cell proliferation and migration through PI3K signal pathway in ovarian cancer

Chen

Duan

et al. 2017

Oncology Reports

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Abstract. ADP-ribosylation factor 1 (ARF1) is a small G protein that regulates many cellular processes such as reorganization of the actin cytoskeleton and is highly expressed in various tumor cells and tissues. However, the role of ARF1 in ovarian cancer progression remains unknown. In the present study, we explored the expression patterns of ARF1 in clinical ovarian cancer samples and adjacent noncancerous tissues. The results revealed that ARF1 overexpressed in EOC tissues and cell lines, compared with the adjacent non-tumorous tissues and normal ovarian cells. In addition, the immunoreactivity of ARF1 was positively correlated with EOC grade and Ki-67 expression. Knockdown of ARF1 expression notably inhibited cell proliferation and migration rate of EOC cells by the auxiliary of PI3K. Taken together, our findings provide new insights into the functional role of ARF1 on EOC cell growth and migration and it may serve as a diagnostic and therapeutic target.

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“…The pathogenesis of OC is concealed, and because of the lack of any effective screening methods to detect the tumors at early stages, the majority of patients are diagnosed at Stage III, some even at Stage IV [28, 29]. Although 80–90% of patients initially respond to chemotherapy, most eventually recur and become chemoresistant [3, 4]. As such, recurrence, chemoresistance and metastasis are the main reasons of mortality in ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Although 80–90% of EOC patients initially respond to first-line chemotherapy agents, platinum and paclitaxel, less than 10–15% remain in complete remission and most patients recur within 5 years [2]. Although a number of patients present with high initial responsiveness to chemotherapy, survival rates still remain low due to later drug resistance and cancer recurrence; and by then, fewer therapeutic options are available and the attention focuses on prolonging patient life expectancy [3, 4]. Therefore, it is imperative to elucidate more targeted treatments.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival

Alvero

et al. 2016

Oncotarget

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Ovarian carcinoma is the most lethal gynecologic tumor worldwide. Despite having developed molecular diagnostic tools and targeted therapies over the past few decades, patient survival is still quite poor. Numerous studies suggest that microRNAs are key regulators of many fundamental biological processes, including neoplasia and tumor progression. miR-222 is one of those miRNAs that has attracted much attention for its multiple roles in human diseases, especially cancer. The potential role of microRNAs in ovarian cancer has attracted much attention in recent years. Some of these microRNAs have been suggested as potential therapeutic targets for EOC patients. In this study, we sought to investigate the biologic functions of miR-222-3p in EOC carcinogenesis. Herein, we examined the expression of miR-222-3p in EOC patients, mouse models and cell lines, and found that higher expression of miR-222-3p was associated with better overall survival in EOC patients, and its level was negatively correlated with tumor growth in vivo. Furthermore, in-vitro experiments indicated that miR-222-3p inhibited EOC cell proliferation and migration, and decreased the phosphorylation of AKT. We identified GNAI2 as a target of miR-222-3p. We also found that GNAI2 promoted EOC cell proliferation, and is an activator of the PI3K/AKT pathway. We describe the characterization of a novel regulatory axis in ovarian cancer cells, miR-222-3p/GNAI2/ AKT and its potential application as a therapeutic target for EOC patients.

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Role of antibodies in diagnosis and treatment of ovarian cancer: Basic approach and clinical status

Cited by 52 publications

References 146 publications

Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity

Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity

Overexpression of ARF1 is associated with cell proliferation and migration through PI3K signal pathway in ovarian cancer

MicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival

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