Track topics on Twitter Track topics that are important to you
The goal of this study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre- and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS) (p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: International journal of cancer
High-grade serous carcinoma (HGSC) is the most common histological subtype of ovarian carcinoma. Somatic mutation of tumor protein 53 (TP53) is a hallmark of tubo-ovarian HGSC and is observed in almos...
Immunostaining for p53 is widely but variably used when diagnosing endometrial carcinoma (EC). Mutant-pattern p53 staining can support a diagnosis of serous carcinoma, and also serve as a surrogate te...
The long-term risk of high-grade dysplasia (HGD) and colorectal cancer (CRC) following low-grade dysplasia (LGD) in inflammatory bowel disease (IBD) patients is relatively unknown. We aimed to determi...
LINE-1 (L1) retrotransposons are mobile genetic elements capable of "copy-and-pasting" their own sequences into random genomic loci and one of the proteins it uses to achieve mobility is LINE-1 open r...
Molecular cancer subtyping is an important tool in predicting prognosis and developing novel precision medicine approaches. We developed a novel platform-independent gene expression-based classificati...
Tumor response to NAC predicts survival and can be considered a surrogate prognostic marker. Three tiered chemotherapy response score (CRS) of omental tissue sections showed a significant ...
The objective of this protocol is to characterize advanced cancer patients' responses to learning their secondary findings arising from tumor genomic profiling, and the process and outcome...
The goal of this clinical research study is to learn if fulvestrant and palbociclib can help to control low-grade serous ovarian cancer. The safety of this drug combination will also be st...
The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and PLD chemotherapy regimen in patients with platinum-resistant recurrent high grade se...
Uterine serous carcinoma (USC) accounts for up to 40% of endometrial cancer-related deaths. Patients with USC share many genomic and clinical characteristics with patients who has serous o...
A tumor of both low- and high-grade malignancy. The low-grade grow slowly, appear in any age group, and are readily cured by excision. The high-grade behave aggressively, widely infiltrate the salivary gland and produce lymph node and distant metastases. Mucoepidermoid carcinomas account for about 21% of the malignant tumors of the parotid gland and 10% of the sublingual gland. They are the most common malignant tumor of the parotid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575; Holland et al., Cancer Medicine, 3d ed, p1240)
Advanced technology that is costly, requires highly skilled personnel, and is unique in its particular application. Includes innovative, specialized medical/surgical procedures as well as advanced diagnostic and therapeutic equipment.
Pregnancy in which the mother and/or FETUS are at greater than normal risk of MORBIDITY or MORTALITY. Causes include inadequate PRENATAL CARE, previous obstetrical history (ABORTION, SPONTANEOUS), pre-existing maternal disease, pregnancy-induced disease (GESTATIONAL HYPERTENSION), and MULTIPLE PREGNANCY, as well as advanced maternal age above 35.
Neoplasms of the thin serous membrane that envelopes the lungs and lines the thoracic cavity. Pleural neoplasms are exceedingly rare and are usually not diagnosed until they are advanced because in the early stages they produce no symptoms.
A malignant epithelial tumor of glandular tissue, especially the salivary glands, characterized by acini with mucus-producing cells and by the presence of malignant squamous elements. Most mucoepidermoid tumors are low-grade lesions readily cured by adequate excision. They may appear in any age group. They grow slowly. If high-grade, they behave aggressively, widely infiltrating the salivary gland and producing lymph node and distant metastases. (Dorland, 27th ed; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575)
Ovarian Cancer is cancer that starts in the female reproductive organs, the ovaries. It is the fifth most common cancer among women. Women at risk of Ovarian Cancer are those who have had few children (or had children at an older age), carriers o...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...