Recurrent Ovarian Cancer Research Articles

Cytoreductive Surgery Plus HIPEC in Recurrent or Newly Diagnosed Advanced Epithelial Ovarian Cancer: a Meta-analysis.

In 2024, two randomized controlled trials (RCTs) were published, providing new high-quality evidence on HIPEC in epithelial ovarian cancer (EOC). Updating data on progression-free survival (PFS) and adverse events could offer a clearer understanding of the benefits and risks of HIPEC combined with cytoreductive surgery (CRS), with or without prior neoadjuvant chemotherapy (NACT). An electronic search was conducted using PubMed, Web of Science, EBSCO, and CENTRAL up to 23 November 2024. We only included RCTs reporting PFS and adverse events of interval or secondary CRS, with or without HIPEC, in newly diagnosed or recurrent EOC. The meta-analysis included six RCTs. The addition of HIPEC to surgery significantly improved PFS in patients with newly diagnosed advanced-stage EOC who received NACT (HR 0.59; 95% CI 0.39-0.88; p = 0.01). No significant difference in PFS was observed between secondary CRS plus HIPEC and CRS alone in recurrent ovarian cancer without prior NACT (HR 1.22; 95% CI 0.82-1.83; p = 0.32). Regarding adverse events, a decrease in platelet count of any grade was more frequent in the HIPEC group (p = 0.03). The overall risk of acute kidney failure (AKF) was 10.6%, with a significantly higher incidence compared with CRS alone (p = 0.003). The addition of HIPEC to CRS significantly improved PFS compared with surgery alone in patients with advanced EOC who received NACT. However, the treatment was associated with a higher incidence of AKF, which occurred in 10.6% of patients who underwent HIPEC.

Development and validation of a nomogram to predict recurrence in epithelial ovarian cancer using complete blood count and lipid profiles

ObjectiveOvarian cancer is one of the most lethal gynecological malignancies. This study aimed to evaluate the prognostic significance of complete blood count (CBC) and lipid profile in patients with optimally debulked epithelial ovarian cancer (EOC) and develop a nomogram model to predict recurrence-free survival (RFS).MethodsThis retrospective study analyzed patients diagnosed with EOC between January 2018 and June 2022.ResultsA total of 307 patients were randomly divided into training and validation sets in a ratio of 7:3. Grade, International Federation of Gynecology and Obstetrics (FIGO) stage, platelet-to-lymphocyte ratio, red blood cell distribution width-coefficient of variation, triglycerides, and human epididymal protein 4 were identified as independent prognostic factors. The novel nomogram displayed a good predictive performance, with a concordance index (C-index) of 0.787 in the training group and 0.807 in the validation group. The areas under the curve for 1-, 3-, and 5-year RFS were 0.770, 0.881, and 0.904, respectively, in the training group, and 0.667, 0.906, and 0.886, respectively, in the validation group. The calibration curves exhibited good concordance between the predicted survival probabilities and actual observations. Time-dependent C-index curves, integrated discrimination improvement, net reclassification index, and decision curve analysis showed that the nomogram outperformed FIGO staging.ConclusionThis study established and validated a nomogram combining CBC and lipid profiles to predict RFS in patients with optimally debulked EOC, which is expected to aid gynecologists in individualized prognosis assessment and clinical management.

SOLO3 Overall Survival Data: The Final Nail in the Coffin for PARP Inhibitor Monotherapy in gBRCA-Mutated, Previously Treated Recurrent Ovarian Cancer?

SOLO3 Overall Survival Data: The Final Nail in the Coffin for PARP Inhibitor Monotherapy in gBRCA-Mutated, Previously Treated Recurrent Ovarian Cancer?

CHIPOR: gaps in recurrent ovarian cancer management

CHIPOR: gaps in recurrent ovarian cancer management

A comprehensive comparison of PARP inhibitors as maintenance therapy in platinum-sensitive recurrent ovarian cancer: a systematic review and network meta-analysis.

PARP inhibitors (PARPis) have shown promising effectiveness for ovarian cancer. This network meta-analysis (PROSPERO registration number CRD42024503390) comprehensively evaluated the effectiveness and safety of PARPis in platinum-sensitive recurrent ovarian cancer (PSROC). Articles published before January 6, 2024 were obtained from electronic databases. The study assessed and compared survival outcomes including overall survival (OS), progression-free survival (PFS), second progression-free survival (PFS2), time to first subsequent treatment (TFST), time to second subsequent treatment (TSST), and chemotherapy-free interval (CFI). Additionally, safety outcomes were investigated, specifically focusing on grade 3-4 treatment-emergent adverse effects (TEAEs). The evaluation of OS and PFS was also conducted based on the BRCA and HRD (homologous recombination deficiency) statuses. Six randomized controlled trials were examined and the four PARPis (olaparib, niraparib, rucaparib and fuluzolparib) have been found to significantly increase the PFS in entire population as well as in subgroups of HRD and BRCAm (BRCA mutation). Only olaparib demonstrated a substantial improvement in OS compared to placebo in entire population (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.60-0.90), as well as in the subgroup of BRCAm. All analyzed PARPis had significant efficacy in prolonging PFS2, TFST, TSST and CFI. For safety concerns, PARPis could significantly increase incidence of TEAEs (grade3-4), while olaparib had least haematological TEAEs (grade3-4) events compared to other PARPis. All included PARPis showed various degrees of benefit in survival outcomes and safety profile was acceptable for PSROC patients. Among them olaparib had the best performance in both efficacy and safety.

Niraparib Maintenance Therapy in Patients with Platinum-Sensitive Recurrent Ovarian Cancer: Real-World Experience at Hospitals in Spain.

The reported benefit of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance in patients with newly diagnosed and platinum (Pt)-sensitive recurrent ovarian cancer (OC) included in randomized clinical trials needs to be corroborated in a less selected population. The aim is to increase the evidence on niraparib in a real-world setting. This is a retrospective observational study including women with platinum-sensitive relapsed high-grade serous OC who started niraparib maintenance between August 2019 (marketing data, Spain) and May 2022. Patients received ≥ 2 previous lines of therapy with complete or partial response to prior chemotherapy. Patient characteristics, niraparib dose, adequacy of dose individualization, effectiveness (progression-free survival [PFS] and overall survival), safety, and economic savings with an individualized starting dose (ISD) strategy were assessed. The study included 217 patients with a median of 8.9 months of niraparib duration: breast cancer gene (BRCA) wild-type OC, 70%; two prior treatment lines, 49%; Research on Adverse Drug Events and Reports (RADAR) criteria, 82% (receiving mainly 200 mg of niraparib, 79%). Median PFS was 10.8 months (95% confidence interval [CI], 8.4-14.8) without statistically significant differences based on starting dose strategy, contrary to what was observed on the basis of prior lines, response to prior chemotherapy, BRCA mutational status, and International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis. The last three variables also showed a statistically significant predictive prognostic value for effectiveness. Dose interruptions due to toxicity were required in 7% of patients, and dose adjustments in 56% were mainly due to hematologic toxicities. The actual dose of niraparib reveals economic savings versus the theoretical cost. This large real-world analysis corroborates the tolerability and activity of niraparib maintenance for platinum-sensitive recurrent OC and economic savings.

Activating the cGAS-STING Pathway by Manganese-Based Nanoparticles Combined with Platinum-Based Nanoparticles for Enhanced Ovarian Cancer Immunotherapy.

Recent research has demonstrated that activating the cGAS-STING pathway can enhance interferon production and the activation of T cells. A manganese complex, called TPA-Mn, was developed in this context. The reactive oxygen species (ROS)-sensitive nanoparticles (NPMn) loaded with TPA-Mn are developed. NPMn activates the cGAS-STING pathway via cGAS activation (i.e., 1.6-fold enhancement of P-STING), which in turn increases the secretion of pro-inflammatory cytokines (e.g., TNF-α, IL-6, and IL-2). This promotes dendritic cell maturation, enhances the infiltration of cytotoxic T lymphocytes, and reduces the percentage of immunosuppressive regulatory T cells. In addition, it is crucial to emphasize that cisplatin-induced DNA damage can potentially trigger activation of the cGAS-STING pathway. NPMn, in combination with low-dose NPPt, a carrier of a Cis(IV) prodrug capable of causing DNA damage, augments the cGAS-STING pathway activation and significantly activates the tumor immune microenvironment (TIME). Furthermore, combined with anti-PD-1 antibody, NPPt+NPMn shows synergistic efficacy in both ovarian cancer peritoneal metastases and recurrence models. It not only effectively eliminates tumors but also induces a strong immune memory response, providing a promising strategy for the clinical management of ovarian cancer. This work offers a design of manganese-based nanoparticles for immunotherapy.

Association of blood group types and clinico-pathological features of gynecological cancers (GCs)

BackgroundGynecological cancers (GCs) affect the reproductive system of females, and are of multiple types depending on the affected organ most common of which are cervical, endometrial, ovarian cancers. Among different risk factors for GCs, ABO blood group system is considered as one of the pivotal contributing factors for increased susceptibility of GCs. The aim of our study was to report on the demographics of GC patients and to investigate the relationship between the ABO blood group system and the risk of acquiring GC in our population.MethodsThe current retrospective cross-sectional study was carried out between the years of 2016 and 2023. The sample included all the patients having age > 18 with a record of blood group and confirmed histological or cytological diagnosis as per International Federation of Gynecology and Obstetrics (FIGO) guidelines. A comprehensive review of the charts was conducted to gather data including demographics, tumor characteristics, comorbidities, adverse effects, and treatment methods.ResultsA total of 543 female patients were included in the study. The mean age of patients was 61.6. The three most common BG in our GC cases were as O + (43.8%), followed by A + (26%), and B + (15.5%). Among comorbidities, hypertension (HTN), diabetes mellitus (DM), dyslipidemia were the top three affecting GC patients. A significant association (p < 0.05) between ABO BG and serous histology in endometrial cancer was found. ABO blood group and fallopian cancer showed a significant relationship between serous histology and B blood group (p < 0.05). For ovarian cancer a significant association between AB blood group and recurrence rates were found (p < 0.05). In case of the patient dependent GCs, a significant association between ovarian cancers and recurrence, fallopian tube cancers and adverse events and survival status, vaginal/vulval cancers and TNM stage and mixed GCs and tumor type (carcinoma) was observed (P < 0.05). Furthermore, multinomial analysis between various confounding factors and GCs revealed that the risk of Cervical, Endometrial and Ovarian cancers to be significant for Type B BG (P < 0.05).ConclusionOur study found that O + BG was the most prevalent among our population. Furthermore, there was a significant association between BG B and endometrial and serous histology in fallopian tube and between BG AB and ovarian malignancies, respectively. Additionally, multinomial analysis revealed higher risk of Cervical, Endometrial and Ovarian cancers for Type B BG (P < 0.05).

P0469 Impact of gynecologic malignancy on ileal pouch-anal anastomosis survival: a matched case-control study

Abstract Background Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard operative treatment for patients with medically refractory inflammatory bowel disease or familial adenomatous polyposis requiring colectomy. In patients who develop malignancy after IPAA, chemoradiation has been shown to increase the risk of pouch failure in small studies. We aimed to describe pouch survival in patients who underwent surgery for gynecologic malignancy (GYN-Ca). Methods We retrospectively reviewed adults who underwent IPAA and developed gynecologic cancer afterwards between 2000 and 2023. Patients with IPAA and GYN-Ca were matched using 1:5 nearest neighbor propensity score matching to control patients with history of IPAA only, on age, year of IPAA, colorectal diagnosis, and procedure. Demographics, operative data, complications, and pouch survival were collected. Results We identified 15 patients diagnosed with GYN-Ca after IPAA who underwent surgery (Table 1). The most common GYN-Ca was endometrial cancer (53%); overall, 14 (93.3%) underwent hysterectomy, while 1 (6.7%) underwent salpingo-oophorectomy; 80% had no short-term postoperative complications. After GYN-Ca in IPAA patients, median overall survival was 51 (21-106) months; median disease-free survival was 41.3 (8-106) months. Pouch failure was seen in 5 (33%) patients, of these, 2 patients (40%) had pouch revision, 2 patients (40%) had pouch excision with permanent end ileostomy and 1 patient (20%) had only permanent end ileostomy. Etiology of pouch failure included radiation enteritis of the pouch (n=2, 40%), afferent limb syndrome from IPAA stenosis (n=1, 20%), inlet obstruction due to Crohn’s stricture (n=1, 20%), and recurrent anastomotic leak secondary to invasive ovarian cancer recurrence (n=1, 20%). After matching, 75 control patients were included for a total of 90 unique patients. The pouch failure rate in the Gyn-Ca and matched control groups were 33% vs. 5.3%, p=0.002, respectively. Kaplan-Meier survival analysis (Figure 1) showed a hazard ratio for pouch failure in GYN-Ca patients of 2.34 (p=0.18, robust SE 0.63) compared to matched control patients, a clinically but not statistically significant result likely due to lack of power. Conclusion In experienced hands, surgery for gynecologic malignancy in pouch patients was safe with an accepted rate of post-operative complications. However, the patients who suffered recurrence or underwent chemoradiation were at increased risk of pouch failure compared to healthy control pouch patients. Patients who develop gynecologic malignancy after IPAA should be monitored closely for pouch dysfunction using a multidisciplinary approach to optimize pouch survival after pelvic surgery.

Controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: study protocol for a randomised controlled trial

IntroductionMultimodal anticancer therapies greatly damage the fertility of breast cancer patients, which raises urgent demand for fertility preservation. The standard options for fertility preservation are oocyte and embryo cryopreservation; both...

Prognostic Factors After the First Recurrence of Ovarian Cancer.

Objective: Ovarian cancer is the fifth most frequent tumor in women and the second most common gynecological cancer. Recurrence of ovarian cancer develops in up to 50-90% of patients within the first five years after diagnosis. Approximately 70% of patients with advanced disease will experience a relapse. The aim of this study was to assess prognostic factors that may predict a higher probability of additional recurrences, as well as their treatment and impact on disease-free and overall survival. Method: A retrospective observational study was conducted on patients diagnosed with recurrent ovarian cancer at the Gynecologic Oncology Unit of Hospital Universitario La Paz (Madrid, Spain) from January 2000 to December 2020. All variables related to the initial treatment, diagnosis, and management of the recurrence were collected and analyzed. Results: Data from 144 patients with recurrent ovarian cancer were analyzed. Statistically significant differences were found in disease-free survival between patients depending on initial tumor staging and primary treatment. Better outcomes were observed in patients with FIGO (International Federation of Gynecology and Obstetrics) stages I-II compared to those with FIGO stages III-IV at diagnosis (p = 0.021), as well as in patients who underwent primary cytoreduction compared to those who received neoadjuvant chemotherapy followed by interval surgery (p < 0.001). The disease-free interval was categorized into three periods, <6 months, 6-12 months, and ≥12 months, with greater survival observed in those with a longer disease-free interval (p < 0.001). After the first recurrence, two factors significantly influenced patient survival: the type of treatment received after the first recurrence (p < 0.001) and the type of chemotherapy regimen (p = 0.001). Complete cytoreduction during primary treatment was an independent prognostic factor and was related to better overall survival in patients where it was achieved (p = 0.004), regardless of the number of recurrences. Conclusions: The prognostic factors with impact on the survival of patients with a first recurrence of ovarian cancer are the following: treatment modality of the primary tumor, treatment modality of the recurrence, type of chemotherapy regimen, and disease-free interval from initial diagnosis to the first recurrence.

SORL1-Mediated EGFR and FGFR4 Regulation Enhances Chemoresistance in Ovarian Cancer.

Recurrent tumors that are resistant to conventional chemotherapy are a major challenge of ovarian cancer treatment. A better understanding of the underlying molecular mechanisms of chemoresistance is critical for developing more effective targeted therapies for ovarian cancer. In this study, we analyzed the transcriptomic profiles of thirteen pairs of matching primary and recurrent ovarian cancers to identify genes that were upregulated in the recurrent tumors. Among these genes, we identified sortilin-related receptor 1 (SORL1) and its role in promoting carboplatin resistance through regulating the stability of epidermal growth factor receptor (EGFR) and fibroblast growth receptor 4 (FGFR4) using ovarian cancer models in vitro and in vivo. We further identified that an anti-SORL1 antibody inhibited the pro-tumor functions of SORL1. Our data showed that a selective inhibitor of FGFR4, FGF401, can improve the therapeutic efficacy of carboplatin in a xenograft mouse model of ovarian cancer. This study has demonstrated the therapeutic potential of targeting the SORL1/FGFR4 pathway to improve the chemoresponse of patients with recurrent and/or resistant ovarian cancer.

Experience of using chemotherapy treatment for the first recurrence of ovarian cancer

Background. The main goal of treating patients with recurrent ovarian cancer is to prolong life and improve its quality. Approaches to the treatment of recurrent ovarian cancer have changed over the past decade. The choice of antitumor drug therapy is determined by the duration of platinum-free interval and the use of targeted therapy with bevacizumab or olaparib. Treatment regimens for relapses are not unified and treatment outcomes are contradictory. Aim: to analyze treatment outcomes of different chemotherapy regimens in patients with the first recurrence of ovarian cancer, depending on the duration of platinum-free interval. Material and Methods. A retrospective analysis of the first recurrence of ovarian cancer in 446 patients treated at the Primorsky Regional Oncology Center in the period 2004–2021 was carried out. All patients were divided into two groups depending on the treatment option for relapse: repeated cytoreduction followed by chemotherapy or only second-line chemotherapy, and into four groups depending on the chemotherapy regimens: 1 – platinum and taxane agents; 2 – platinum and taxane agents with bevacizumab; 3 – platinum agents and non-taxane agents with bevacizumab; 4 – monotherapy with non-platinum agents with bevacizumab. Results. Significant advantages in progression-free survival after second-line chemotherapy (PFS-2) were observed in patients with platinum-resistant relapse after the 4th chemotherapy regimen. Patients with platinum-sensitive relapse had the best treatment outcomes after the 3rd chemotherapy regimen and repeated cytoreduction followed by chemotherapy with a platinum-free interval of 6–12 months and 12–24 months with any platinum-containing chemotherapy regimen. In the platinum-free interval of more than 24 months, significant benefits were observed with a combination of platinum and taxane agents + bevacizumab. In the group of patients without surgery, there were significant benefits in all three intervals when prescribing a combination of platinum and non-oxane agents ± bevacizumab. There was a tendency to increase PFS-2 in patients with low-grade serous ovarian carcinoma compared with patients with high-grade serous carcinoma. The best rates of relapse-free survival were noted with maintenance therapy with olaparib. Conclusion. In patients with localized recurrence of ovarian cancer and a platinum-free interval of more than 6 months, it is advisable to perform repeated cytoreduction followed by chemotherapy, taking into account the duration of the platinum-free interval. The administration of PARP inhibitors in the maintenance therapy of platinum-sensitive recurrence of ovarian cancer improves treatment results.

Immunotherapy in Recurrent Ovarian Cancer.

It remains challenging to treat recurrent ovarian cancer effectively as traditional interventions like chemotherapy and surgery have limited long-term efficacy, highlighting an urgent need for innovative approaches. Immunotherapy offers potential advantages in modulating the immune response against tumor cells and has emerged as a promising strategy in ovarian cancer management. This review discusses various immunotherapy modalities, including active and passive immune strategies, for recurrent ovarian cancer. We systematically reviewed recent immunotherapy advances for recurrent ovarian cancer, including the efficacy and mechanisms of single and dual immune checkpoint inhibitors, checkpoint inhibitor combinations with chemotherapy or radiotherapy, anti-angiogenic agents, PARP inhibitors, antibody-drug conjugates (ADC), tumor vaccines, and adoptive cell therapies (ACT). Additionally, we assessed emerging research on biomarkers predictive of immunotherapy responsiveness in ovarian cancer. The findings indicate that immunotherapy, particularly combinations involving immune checkpoint inhibitors and other agents, demonstrates promising efficacy in recurrent ovarian cancer, with some therapies showing enhanced benefits in specific subtypes. The immune microenvironment in platinum-sensitive and -resistant cases exhibits distinct immunological profiles, influencing therapy outcomes. Several potential biomarkers have been identified, potentially aiding in patient stratification and treatment optimization. Immunotherapy significantly advances recurrent ovarian cancer treatment, with various combinations potentially improving outcomes. Further research on predictive biomarkers and immune microenvironment characteristics is crucial for personalizing immunotherapy approaches and enhancing their efficacy in managing recurrent ovarian cancer.

Experience in performing multivisceral resections for pelvic cancer

Background. Treatment of patients with locally advanced pelvic cancer remains challenging. The use of modern surgical techniques has expanded the feasibilities of performing multivisceral resections (MVR) in this category of patients. However, the postoperative period in patients who have undergone MVR is associated with a high risk of developing postoperative complications. The purpose of the study was to assess the short-term and long-term treatment outcomes in patients with locally advanced and multiple-primary pelvic cancer. Material and Methods. From 2009 to 2021, 114 patients treated in the clinics of Cancer Research Institute of Tomsk National Research Medical Center underwent MVR for primary or recurrent rectal cancer (n=40, 35.1 % and n=4, 3.5 %, respectively), female reproductive cancer (endometrial cancer: n=18, 17.1 % and recurrent ovarian cancer: n=18, 17.1 %), primary and recurrent bladder cancer (n=15, 13.2 % and n=2, 1.8 %, respectively), synchronous multiple primary pelvic tumors (n=8, 7.0 %) and extraorgan mesenchymal tumors of the pelvis (n=4, 3.5 %). Paraneoplastic complications were observed in 31 (27.2 %) patients. Invasion to more than 2 adjacent pelvic organs was diagnosed in 52 (45.4 %) cases. Total pelvic evisceration (TPE) was performed in 9 (7.9 %) patients, including 5 (4.4 %) patients who underwent TPE for primary rectal cancer with extensive local spread and 4 (3.5 %) patients who underwent TPE for multiple primary cancer: 2 (1.75 %) for synchronous primary rectal cancer and bladder cancer and 2 (1.75 %) for primary rectal cancer and recurrent bladder cancer. MVR for rectal cancer was the most common (n=101, 88.6 %). Resections with the formation of colorectal anastomosis were performed in 75 (65.8 %) cases and obstructive resections of the rectum were performed in 14 (12.5 %) cases. Urinary tract surgeries were performed in 66 (57.5 %) cases. One-stage plastic surgery of the resected segment as a transposition of one or both ureters into the bottom of the bladder was performed in 22 (19.3 %) cases. Heterotopic and orthotopic plastic surgery of the bladder was performed in 19 (16.6 %) and 5 (4.4 %) cases, respectively. Combined uterine extirpations, including vaginal resection, were performed in 52 (45.4 %) cases. Grade III postoperative complications according to the Clavien–Dindo classification occurred in 18.4 % of cases. Urological complications were the most common (8.7 %). Postoperative mortality rate was 0.8 %. The assessment of the long-term outcomes was carried out using the example of patients with rectal cancer (n=45), as the most homogeneous and largest subgroup. The overall 3-year survival rate was 71.1 % and the relapse-free 3-year survival rate was 60.0 %. Conclusion. Treatment of locally advanced pelvic cancer requires extensive surgeries performed by a multidisciplinary team of surgeons. The immediate results can be assessed as satisfactory. In case of resection of the urinary tract as a component of MVR, regardless of the primary localization of the tumor, primary plastic surgery of the bladder and/or ureters is preferable. Long-term outcomes allow us to consider MVR as a method of choice in the treatment of this group of patients.

Survival analysis of recurrent ovarian cancer under different PARP inhibitor treatment patterns: a single-center retrospective study

Survival analysis of recurrent ovarian cancer under different PARP inhibitor treatment patterns: a single-center retrospective study

Fluence rate-dependent kinetics of light-triggered liposomal doxorubicin assessed by quantitative fluorescence-based endoscopic probe.

Liposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin-phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery. By integrating diffuse reflectance and fluorescence spectroscopy, our approach not only corrects the effects of tissue optical properties but also ensures accurate drug delivery to deep-seated tumors. Preliminary results validate the probe effectiveness in controlled settings, highlighting its potential for future clinical adaptation. This study sets the stage for in vivo applications, enabling the exploration of next-generation treatment paradigms for the management of cancer by optimizing chemotherapy administration with precision and control.

Co-Expression of Dominant-Negative TGF-β Receptor 2 Enhances the Therapeutic Efficacy of Novel TREM1/DAP12-BB-Based CAR-T Cells in Solid Tumours.

Chimeric antigen receptor (CAR) T-cell therapy has exhibited remarkable efficacy in the treatment of haematological malignancies, yet its application in solid tumours is hindered by the immunosuppressive tumour microenvironment (TME). In this study, a novel SS1-TREM1/DAP12-BB CAR-T cell was devised to target ovarian cancer and further engineered to co-express the dominant-negative TGF-β receptor 2 (DNR) to combat CAR-T cell exhaustion in TME. The incorporation of DNR effectively blocked TGF-β signalling, thereby enhancing CAR-T cell survival and antitumor activity in a TGF-β1-rich environment. Invivo evaluations demonstrated that DNR co-expression potentiated the antitumor efficacy of TREM1/DAP12-BB CAR-T cells and conferred resilience against tumour rechallenge. These findings underscore the broad potential of DNR co-expression in CAR design, presenting a novel therapeutic strategy for patients with recurrent ovarian cancer.

Prognostic significance and accuracy of oncologists' estimates of survival time in recurrent ovarian cancer.

We evaluated the accuracy of oncologists' estimates of expected survival time in recurrent ovarian cancer. Oncologists estimated expected survival time at baseline for each patient, who were then followed up for survival time. We hypothesized that oncologists' estimates of expected survival time would be independently significant predictors of survival, unbiased (approximately equal proportions [50%] living longer versus shorter than their expected survival time), or imprecise (<30% within 0.75-1.33 times their observed survival time). We also hypothesized that simple multiples (0.25, 0.5, 2, and 3) of each expected survival time would define ranges that accurately described 3 scenarios for survival time: worst-case (10% of participants with the shortest survival), typical (middle 50%), and best-case (10% with the longest survival) scenarios. There were 898 participants; the median (interquartile range) for expected survival time was 12 months (range; 8-14) and the median for observed survival time was 13 months (range; 12-14). Oncologists' estimates of expected survival time were independently significant predictors of observed survival time (HR 0.96 per month, 95% CI 0.94-0.98, p < .0001). As hypothesized, 55% lived longer than their expected survival time, 45% shorter than their expected survival time, and 23% of estimates of expected survival time were within 0.75 to 1.33 times their observed survival time. Simple multiples of the expected survival time provided ranges that accurately described 3 scenarios for survival time: 7% of patients died within 0.25 times their expected survival time (worst-case), 53% lived between 0.5 and 2 times their expected survival time (typical), and 13% lived longer than 3 times their expected survival time (best case). Oncologists' estimates of expected survival time were independently significant predictors of survival time. Simple multiples of the expected survival time provided accurate ranges for scenarios for survival that are useful for explaining prognosis.

Evaluating the specific STAT3 inhibitor YHO-1701 in ovarian cancer cell lines and patient-derived cell models: efficacy, mechanisms, and therapeutic potential.

Signal transducer and activator of transcription 3 (STAT3) plays key roles in regulating cancer cell proliferation, survival, and metastasis. We aimed to determine the effects of YHO-1701, an oral STAT3 inhibitor, in ovarian cancer (OC). We evaluated the impact of YHO-1701 on cell growth in patient-derived cells (PDCs) and OC cell lines using standard cell proliferation assays. Spheroid models derived from PDCs were assessed using three-dimensional (3D) cell viability assays. Antitumor activity was performed in SKOV3 xenograft mice treated orally administrated YHO-1701 with 20 mg/kg. Changes in STAT3 signaling were analyzed by western blotting. The molecular mechanisms of STAT3 inhibition were investigated by sequencing RNA and analyzing pathways in the SKOV3 using a small interfering RNA targeting STAT3 (STAT3 siRNA) and YHO-1701. YHO-1701 inhibited the growth of OC cell lines by preventing STAT3 dimerization and decreasing the expression of its downstream signaling molecule, survivin. The growth of PDCs and spheroids obtained from patients with primary and recurrent OCs was significantly inhibited. Antitumor effect was observed in the SKOV3 xenograft mice with YHO-1701. YHO-1701 induced apoptosis in OC cells. Additionally, p53 and/or MAPK signaling pathways were upregulated in SKOV3 cells incubated with YHO-1701 and in those with STAT3 siRNA. Our results showed that YHO-1701 suppressed cell growth in PDCs of OC, accompanied by survivin inhibition, and a decrease in the number of peritoneal metastasis in the mice by YHO-1701, compared with those treated with control. Therefore, YHO-1701 could be a promising candidate agent for treating OC.