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Women diagnosed with late-stage ovarian cancer suffer a very high rate of mortality. Accordingly, it is imperative to detect and diagnose the disease as early as possible in its development. Achievement of this aim implies relatively large scale screening of women at an age of clinically significance through assay of biomarkers for disease present in blood or serum. Biosensor detection offers an attractive technology for the automated detection of such species. Among several biomarkers that have been identified that are present in patients with ovarian cancer, the only one that is commonly tested for in clinical use is cancer antigen 125, which is considered to be poor biomarker for the disease. Here, we describe alternative biomarkers which overcome many of the problems associated with cancer antigen 125 such as increased sensitivity and specificity especially in the early stages of the disease and which could be employed successfully in a biosensor format. In particular, we discuss the chemistry of probes for the biomarkers, heat shock protein 10 and lysophosphatidic acid. The challenges presented by the fabrication of biosensor devices for the detection of the cancer, and the limited number of biosensors that have been developed for this purpose are discussed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Electrochemical biosensors are valued for their sensitivity and selectivity in detecting biological molecules. Having the advantage of generating signals that can be directly or indirectly proportional to the concentration of the target analyte, these biosensors can achieve specificity by utilizing a specific biorecognition surface designed to recognize the target molecule. Electrochemical biosensors have garnered substantial attention, as they can be used to fabricate compact, cost-effective devices, making them promising candidates for point-of-care testing (POCT) devices. This study introduces a label-free electrochemical biosensor employing a gold screen-printed electrode (SPE) to detect lysophosphatidic acid (LPA), a potential early ovarian cancer biomarker. We employed the gelsolin–actin system, previously introduced by our group, in combination with fluorescence spectrometry, as a biorecognition element to detect LPA. By immobilizing a gelsolin–actin complex on an SPE, we were able to quantify changes in current intensity using cyclic voltammetry and differential pulse voltammetry, which was directly proportional to the LPA concentration in the solution. Our results demonstrate the high sensitivity of the developed biosensor for detecting LPA in goat serum, with a limit of detection (LOD) and a limit of quantification (LOQ) of 0.9 µM and 2.76 µM, respectively, highlighting its potential as a promising tool for early-stage diagnosis of ovarian cancer. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify and treat patients according to disease stage. LPA is known to target the actin-binding protein gelsolin which is a key regulator of actin filament assembly. Previous studies have shown that the phosphate headgroup of LPA alone is inadequate to bind to the short chain of amino acids in gelsolin known as the PIP2-binding domain. Thus, the molecular-level detail of the mechanism of LPA binding is poorly understood. Here, we model LPA binding to the PIP2-binding domain of gelsolin in the gelsolin-actin complex through extensive ten-microsecond atomistic molecular dynamics (MD) simulations. We predict that LPA binding causes a local conformational rearrangement due to LPA interactions with both gelsolin and actin residues. These conformational changes are a result of the amphipathic nature of LPA, where the anionic phosphate, polar glycerol and ester groups, and lipophilic aliphatic tail mediate LPA binding via charged electrostatic, hydrogen bonding, and van der Waals interactions. The negatively-charged LPA headgroup binds to the PIP2-binding domain of gelsolin-actin while its hydrophobic tail is inserted into actin, creating a strong LPA-insertion pocket that weakens the gelsolin–actin interface. The computed structure, dynamics, and energetics of the ternary gelsolin–LPA–actin complex confirms that a quantitative OC assay is possible based on LPA-triggered actin release from the gelsolin-actin complex. [ABSTRACT FROM AUTHOR]

Purpose: Screening logs have the potential to help oncology clinical trial programs at the site level, as well as trial leaders, address enrollment in real time. Such an approach could be especially helpful in improving representation of racial/ethnic minority and other underrepresented populations in clinical trials. Methods: The National Cancer Institute Community Cancer Centers Program (NCCCP) developed a screening log. Log data collected from March 2009 through May 2012 were analyzed for number of patients screened versus enrolled, including for demographic subgroups; screening methods; and enrollment barriers, including reasons for ineligibility and provider and patient reasons for declining to offer or participate in a trial. User feedback was obtained to better understand perceptions of log utility. Results: Of 4,483 patients screened, 18.4% enrolled onto NCCCP log trials. Reasons for nonenrollment were ineligibility (51.6%), patient declined (25.8%), physician declined (15.6%), urgent need for treatment (6.6%), and trial suspension (0.4%). Major reasons for patients declining were no desire to participate in trials (43.2%) and preference for standard of care (39%). Major reasons for physicians declining to offer trials were preference for standard of care (53%) and concerns about tolerability (29.3%). Enrollment rates onto log trials did not differ between white and black (P = .15) or between Hispanic and non-Hispanic patients (P = .73). Other races had lower enrollment rates than whites and blacks. Sites valued the ready access to log data on enrollment barriers, with some sites changing practices to address those barriers. Conclusion: Use of screening logs to document enrollment barriers at the local level can facilitate development of strategies to enhance clinical trial accrual. [ABSTRACT FROM AUTHOR]