Health Disparities among Patients with Cancer Who Received Molecular Testing for Biomarker-Directed Therapy.

Health disparities present a barrier to successful oncology treatment. The potential for precision oncology to reduce health disparities has not previously been analyzed. We performed a retrospective analysis of 12,627 patients from six major cancer centers whose tumors underwent molecular testing at Caris Life Sciences between 2010 and 2020.

HER2 in Uterine Serous Carcinoma: Testing platforms and implications for targeted therapy.

Objective: HER2 is an important prognostic and therapeutic target in uterine serous carcinoma (USC). Optimal HER2 testing platforms have not been defined and guidelines for testing have changed over time. Our objective is to assess the concordance of HER2 positivity based on chromogenic in situ hybridization (CISH), immunohistochemistry (IHC), and next generation sequencing (NGS) and to determine the rate of downstream mutations that may affect response to HER2 directed therapy.

A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006).

Purpose: The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer.

Methods: This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery.

Molecular profiles of endometrial cancer tumors among Black patients.

Objectives: Disparate outcomes exist between Black and White patients with endometrial cancer (EC). One contributing factor is the disproportionately low representation of Black patients in clinical trials and in tumor molecular profiling studies. Our objective was to investigate molecular profiles of ECs in a cohort with a high proportion of tumors from Black patients.

ONC201 induces the unfolded protein response (UPR) in high- and low-grade ovarian carcinoma cell lines and leads to cell death regardless of platinum sensitivity.

Objectives: Treatment of both platinum resistant high grade (HG) and low-grade (LG) ovarian cancer (OVCA) poses significant challenges as neither respond well to conventional chemotherapy leading to morbidity and mortality. Identification of novel agents that can overcome chemoresistance is therefore critical. Previously, we have demonstrated that OVCA has basal upregulated unfolded protein response (UPR) and that targeting cellular processes leading to further and persistent upregulation of UPR leads to cell death.

Hysteroscopic Morcellation in Endometrial Cancer Diagnosis: Increased Risk?

Study Objective: Operative hysteroscopy requires elevated intrauterine pressures, which could lead to the spread of malignant cells into the peritoneal cavity. Currently, there is a paucity of data analyzing clinical outcomes in endometrial cancer after hysteroscopic morcellation with newer equipment. In this study, we sought to determine whether there are increased rates of positive peritoneal cytology, lymphovascular space invasion, or surgical upstaging in patients undergoing hysteroscopic morcellation compared with alternative endometrial biopsy methods.

Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial.

Background: High-grade serous ovarian cancers show increased replication stress, rendering cells vulnerable to ATR inhibition because of near universal loss of the G1/S checkpoint (through deleterious TP53 mutations), premature S phase entry (due to CCNE1 amplification, RB1 loss, or CDKN2A mRNA downregulation), alterations of homologous recombination repair genes, and expression of oncogenic drivers (through MYC amplification and other mechanisms). We hypothesised that the combination of the selective ATR inhibitor, berzosertib, and gemcitabine could show acceptable toxicity and superior efficacy to gemcitabine alone in high-grade serous ovarian cancer.

Methods: In this multicentre, open-label, randomised, phase 2 study, 11 different centres in the US Experimental Therapeutics Clinical Trials Network enrolled women (aged ≥18 years) with recurrent, platinum-resistant high-grade serous ovarian cancer (determined histologically) and Eastern Cooperative Oncology Group performance status of 0 or 1, who had unlimited previous lines of cytotoxic therapy in the platinum-sensitive setting but no more than one line of cytotoxic therapy in the platinum-resistant setting.

Immune checkpoint expression, microsatellite instability, and mutational burden: Identifying immune biomarker phenotypes in uterine cancer.

Objectives: Increasing grade of endometrioid endometrial cancer (EEC) is associated with aggressive behavior and poor prognosis. The traditional classification system is limited in its ability to guide treatment planning and prognostication. We identify distinct immune biomarker phenotypes using known markers of immunogenicity to identify patients who may benefit from immune therapy (IT).

Miniaturized phased-array ultrasound and photoacoustic endoscopic imaging system.

Visualization and detection of early-stage gynecological malignancies represents a challenge for imaging due to limiting factors including tissue accessibility, device ease of use, and accuracy of imaging modalities. In this work, we introduce a miniaturized phased-array ultrasound and photoacoustic endoscopic probe which is capable of providing structural, functional, and molecular data for the characterization of gynecologic disease. The proposed probe consists of a 64-element ultrasound phased-array transducer coupled to a fiber-optic light delivery system for co-registered ultrasound and photoacoustic imaging.

Management of squamous cell vulvar cancer: a review.

Squamous cell vulvar cancer is a rare gynecologic malignancy. Standard treatment for early stage disease consists of wide radical excision of the primary tumor with inguinal-femoral lymphadenectomy or sentinel lymph node mapping/biopsy. Because of the general paucity of patients with advanced vulvar cancer, there is no standard therapy for advanced disease and therefore treatment should be individualized.

Chemotherapy of vulvar cancer: a review.

Squamous cell carcinoma of the vulva is a rare disease with good prognosis if diagnosed early. The standard primary therapy is surgery. Neoadjuvant radiation or chemotherapy has been used to achieve resectability of the tumor and to decrease the radicality of the surgery.

Clinical and pathologic characteristics of serous carcinoma confined to the endometrium: a multi-institutional study.

The objective of this study was to analyze the clinical and pathologic factors in patients with uterine serous carcinoma confined to the endometrium. A total of 236 uterine serous carcinoma patients from the pathology databases of 4 large academic institutions were included in the study. Clinical and pathologic variables were analyzed, including patient demographics, tumor size (≤2 vs.

Merkel cell carcinoma in a patient with noninvasive vulvar Paget's disease.

We present the first case of inguinal Merkel cell carcinoma of unknown primary origin in a patient with vulvar Paget's disease. Correlation with immune suppression of both entities warrants further investigation. Additionally, this case highlights the value of ultrasound scanning in the detection of inguinal metastasis.

Lysine residues Lys-19 and Lys-49 of beta-catenin regulate its levels and function in T cell factor transcriptional activation and neoplastic transformation.

Wnt signaling regulates cell fate determination, proliferation, and survival, among other processes. Certain Wnt ligands stabilize the beta-catenin protein, leading to the ability of beta-catenin to activate T cell factor-regulated genes. In the absence of Wnts, beta-catenin is phosphorylated at defined serine and threonine residues in its amino (N) terminus.