Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer Part 2: Medical Perspectives

Abstract

High-grade serous ovarian cancer (HGSOC) is the most frequent and aggressive form of ovarian cancer, representing an important challenge for clinicians. Half of HGSOC cases have homologous recombination deficiency (HRD), which has specific causes (mainly alterations in BRCA1/2, but also other alterations encompassed by the BRCAness concept) and consequences, both at molecular (e.g., genomic instability) and clinical (e.g., sensitivity to PARP inhibitor) levels. Based on its prevalence and clinical impact, HRD status merits investigation. To date, three PARP inhibitors have received FDA/EMA approval. For some approvals, the presence of specific molecular alterations is required. Three companion diagnostic (CDx) assays based on distinct technical and medical considerations have received FDA approval to date. However, their use remains controversial due to their technical and medical limitations. In this companion and integrated review, we take a “bench-to-bedside” perspective on HRD definition and evaluation in the context of HGSOC. Part 1 of the review adopts a molecular perspective regarding technical considerations and the development of CDx. Part 2 focuses on the clinical impact of HRD evaluation, primarily through currently validated CDx and prescription of PARP inhibitors, outlining achievements, limitations and medical perspectives.

Alterations in Homologous Recombination-Related Genes and Distinct Platinum Response in Metastatic Triple-Negative Breast Cancers: A Subgroup Analysis of the ProfiLER-01 Trial

“…Thirdly, it is now well-known that HRD status may be assessed through diverse companion diagnostic assays; they nevertheless do not overlap perfectly [ 7 ]. The MyChoice ® assay has been shown to represent the current gold standard in ovarian cancer as a prerequisite to PARPi challenge [ 31 ]. As such, it would have been interesting to analyze the potent correlation between the molecular alterations observed in our study and the associated HRD score.…”

Comparative Sensing and Judgment Control System for Temperature Maintenance for Optimal Treatment in Hyperthermic Intraperitoneal Chemotherapy Surgery

“…Chemotherapy is used simultaneously to reduce the possibility of recurrence, but patients face difficulties during the treatment process due to side effects [ 1 ]. In order to pursue methods to promote the inhibition of cancer cell growth, treatment methods currently used in medical institutions include HIFU (high-intensity frequency ultrasound) treatment, laser treatment, and high-frequency treatment [ 2 , 3 , 4 , 5 ].…”

The Design of an Automatic Temperature Compensation System through Smart Heat Comparison/Judgment and Control for Stable Thermal Treatment in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Surgery

“…However, due to its side effects, patients experience difficulties during treatment. Thus, new treatment methods for eliminating the probability of recurrence within 5 years have been studied and are currently being used in many medical institutions [ 1 , 2 , 3 , 4 , 5 , 6 ]. Most of the thermal death methods for tumors include HIFU (High-Intensity Frequency Ultrasonic) treatment, laser treatment, and radiofrequency treatment [ 3 , 4 , 5 , 6 ].…”

“…Thus, new treatment methods for eliminating the probability of recurrence within 5 years have been studied and are currently being used in many medical institutions [ 1 , 2 , 3 , 4 , 5 , 6 ]. Most of the thermal death methods for tumors include HIFU (High-Intensity Frequency Ultrasonic) treatment, laser treatment, and radiofrequency treatment [ 3 , 4 , 5 , 6 ]. Among them, the high-frequency treatment causes hyperthermia by an antenna that heats through radio and microwave radiation and damages cancer cells with heat.…”