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Comprehensive profiling of EGFR/HER receptors for personalized treatment of gynecologic cancers.

ABSTRACT: The primary gynecologic cancers include cancers of the endometrium, ovary, and cervix. Worldwide, cervical cancer is the most common gynecologic cancer, whereas endometrial cancer is the most common in the US. Ovarian cancer is the fifth most deadly cancer in women, with 5-year survival rates for advanced disease at only 27 %. As such, there is an urgent need for reliable screening tools and novel targeted therapeutic regimens for these malignancies. The epidermal growth factor receptor (EGFR)/human EGFR (HER) family of receptors has been associated with the development and progression of many solid tumors. Despite clear roles for these receptors in other cancers, the expression of HER family members in gynecologic cancers and their relationship with disease stage, grade, and response to treatment remain controversial. In this review, we describe the existing evidence for the use of HER family members as diagnostic and prognostic indicators as well as their potential as therapeutic targets in gynecologic cancers.

SUBMITTER: Reyes HD

PROVIDER: S-EPMC3969446 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Comprehensive profiling of EGFR/HER receptors for personalized treatment of gynecologic cancers.

Reyes Henry D HD Thiel Kristina W KW Carlson Matthew J MJ Meng Xiangbing X Yang Shujie S Stephan Jean-Marie JM Leslie Kimberly K KK

Molecular diagnosis & therapy 20140401 2

The primary gynecologic cancers include cancers of the endometrium, ovary, and cervix. Worldwide, cervical cancer is the most common gynecologic cancer, whereas endometrial cancer is the most common in the US. Ovarian cancer is the fifth most deadly cancer in women, with 5-year survival rates for advanced disease at only 27 %. As such, there is an urgent need for reliable screening tools and novel targeted therapeutic regimens for these malignancies. The epidermal growth factor receptor (EGFR)/h ...[more]

PMID: 24403167

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Project description:BackgroundHigh-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools.Methods and findingsTumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival.ConclusionsDetection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic dilemma and a potential critical inflection point in precision medicine. This study suggests that the use of personalized ctDNA biomarkers in gynecologic cancers can identify the presence of residual tumor while also more dynamically predicting response to treatment relative to currently used serum and imaging studies. Of particular interest, ctDNA was an independent predictor of survival in patients with ovarian and endometrial cancers. Earlier recognition of disease persistence and/or recurrence and the ability to stratify into better and worse outcome groups through ctDNA surveillance may open the window for improved survival and quality and life in these cancers.

Dataset Information

Comprehensive profiling of EGFR/HER receptors for personalized treatment of gynecologic cancers.

Publications

Comprehensive profiling of EGFR/HER receptors for personalized treatment of gynecologic cancers.

Similar Datasets

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