Sucrose Nonfermenting-Related Kinase Expression Is Related to a Metabolic Switch in Ovarian Cancer Cells That Results in Increased Fatty Acid Oxidation.

Ovarian cancer frequently metastasizes to the omentum, which is primarily comprised of adipocytes. Our previous study found that sucrose nonfermenting-related kinase (SNRK) expression is lower in advanced-stage compared with early-stage ovarian cancer tissue. In this study, SNRK knockdown was performed in ovarian cancer cell lines using lentiviral transduction and resulted in decreased cell proliferation, increased invasion, and a switch in metabolism to increased fatty acid oxidation (FAO). Our data suggest that SNRK works as a metabolic checkpoint that allows for oxidative phosphorylation and prevents FAO during a time of rapid tumor growth.

Who will be readmitted? Evaluation of the laparoscopic hysterectomy readmission score in a gynecologic oncology population undergoing robotic-assisted hysterectomy.

OBJECTIVES: The laparoscopic hysterectomy readmission score (LHRS) was created to identify patients for whom same day discharge (SDD) after minimally invasive hysterectomy (MIH) may not be advisable and includes diabetes, chronic obstructive pulmonary disease, disseminated cancer, chronic steroid use, bleeding disorder, length of surgery, and any postoperative complication prior to discharge. We evaluated the performance of the score at predicting readmission in a gynecologic oncology population, and additionally sought to determine if any factors known prior to surgery could replace those that are not known until the time of surgery (operative time and postoperative complication). METHODS: This was a single-institution retrospective cohort study of women undergoing robotic hysterectomy by a gynecologic oncologist in 2018. Associations between pre-operative, operative and post-operative factors and 30-day readmission, SDD and postoperative complications were assessed using logistic regression. RESULTS: The 30-day readmission rate among the 423 women in the cohort was 4.5% and 1.9% in those undergoing SDD. Readmission rates by LHRS were: score 1 (4.9%), score 2 (7.8%), score 3 (13.6%), score 4 (16.7%). Patients with a LHRS of ≥3 had higher odds of readmission compared to those with a lower score (OR 4.20, p = 0.02). Infectious morbidity accounted for the majority of postoperative complications, emergency room visits and readmissions. We did not identify preoperative factors to replace the intra- and post-operative factors used in the score. CONCLUSIONS: The readmission rate following MIH is low, and a LHRS of ≥3 is associated with increased risk of readmission. Our findings support the applicability of the LHRS to a gynecologic oncology population; addressing risk factors for postoperative infection or closer follow up for patients with a LHRS ≥3 could reduce postoperative readmissions.

A School Nurse Application of the ECHO Model.

Type I diabetes (T1D) is one of the most common childhood diseases and Type 2 diabetes (T2D) is increasing at alarming rates. Given that children spend a great percentage of their time in school, this setting is a critical environment for models of care that lead to better management of this and other health conditions. The School Nurses Managing Diabetes Care ECHO was offered to Colorado school nurses to build their capacity in providing evidence-based management of T1D. The purpose of this effort was to (1) determine whether or not the model could be used as a tool of collaboration and dissemination for school nurses across Colorado and (2) assess the effectiveness of the "School Nurses Managing Diabetes Care" ECHO learning series. Post-series survey results demonstrated a 25% increase in self-efficacy ratings, moving learners from "average among my peers" toward "competent." Additionally, all respondents planned to make one or more practice changes to improve care for students with T1D. Expanding the use of the ECHO model to implement intensive management of children and youth with T1D is critically important as rates of this and other chronic conditions continue to increase.

Surgical outcomes among elderly women with endometrial cancer treated by laparoscopic hysterectomy: a NRG/Gynecologic Oncology Group study.

OBJECTIVE: Tolerance of and complications caused by minimally invasive hysterectomy and staging in the older endometrial cancer population is largely unknown despite the fact that this is the most rapidly growing age group in the United States. The objective of this retrospective review was to compare operative morbidity by age in patients on the Gynecologic Oncology Group Laparoscopic Surgery or Standard Surgery in Treating Patients With Endometrial Cancer or Cancer of the Uterus (LAP2) trial. STUDY DESIGN: This is a retrospective analysis of patients from Gynecologic Oncology Group LAP2, a trial that included clinically early-stage uterine cancer patients randomized to laparotomy vs laparoscopy for surgical staging. Differences in the rates and types of intraoperative and perioperative complications were compared by age. Specifically complications between patients <60 vs ≥60 years old were compared caused by toxicity analysis showing a sharp increase in toxicity starting at age 60 years in the laparotomy group. RESULTS: LAP2 included 1477 patients ≥60 years old. As expected, with increasing age there was worsening performance status and disease characteristics including higher rates of serous histology, high-stage disease, and lymphovascular space invasion. There was no significant difference in lymph node dissection rate by age for the entire population or within the laparotomy or laparoscopy groups. Toxicity analysis showed a sharp increase in toxicity seen in patients ≥60 years old in the laparotomy group. Further analysis showed that when comparing laparotomy with laparoscopy in patients <60 years old vs ≥60 years old and controlling for race, body mass index, stage, grade, and performance status, patients <60 years old undergoing laparotomy had more hospital stays >2 days (odds ratio, 17.48; 95% confidence interval, 11.71-27.00, P < .001) compared with patients <60 years old undergoing laparoscopy. However, when comparing laparotomy with laparoscopy in patients ≥60 years old, in addition to hospital stay >2 days (odds ratio, 12.77; 95% confidence interval, 8.74-19.32, P < .001), there were higher rates of the following postoperative complications: antibiotic administration (odds ratio, 1.63; 95% confidence interval, 1.24-2.14, P < .001), ileus (odds ratio, 2.16; 95% confidence interval, 1.42-3.31, P <0.001), pneumonias (odds ratio, 2.36; 95% confidence interval, 1.01-5.66, P = .048), deep vein thromboses (odds ratio, 2.87; 95% confidence interval, 1.08-8.03, P = .035), and arrhythmias (odds ratio, 3.21; 95% confidence interval, 1.60-6.65, P = .001) in the laparotomy group. CONCLUSION: Laparoscopic staging for uterine cancer is associated with decreased morbidity in the immediate postoperative period in patients ≥60 years old. These results allow for more accurate preoperative counseling. A minimally invasive approach to uterine cancer staging may decrease morbidity that could affect long-term survival.

Sucrose Non-Fermenting Related Kinase Expression in Ovarian Cancer and Correlation with Clinical Features.

Sucrose non-fermenting related kinase (SNRK) is a serine/threonine kinase known to regulate cellular metabolism and adipocyte inflammation. Since alterations in adipocyte metabolism play a role in ovarian cancer metastasis, we investigated the expression of SNRK in benign and malignant human ovarian tissue using immunohistochemistry and qPCR. The number of SNRK positive (+) nuclei is increased in malignant tissue compared to benign tissue (21.03% versus 14.90%, p < .0431). The most strongly stained malignant SNRK+ nuclei were stage 1 compared to stage 2-4 disease. Differential expression of SNRK in early versus late stage disease suggests specific roles for SNRK in ovarian cancer metastasis.

Pathologic and Treatment Outcomes Among a Geriatric Population of Endometrial Cancer Patients: An NRG Oncology/Gynecologic Oncology Group Ancillary Data Analysis of LAP2.

OBJECTIVES: Elderly endometrial cancer patients have worse disease-specific survival than their younger counterparts, but the cause for this discrepancy is unknown. The goal of this analysis is to compare outcomes by age in a fully staged elderly endometrial cancer population. METHODS/MATERIALS: This is an analysis of patients on Gynecologic Oncology Group Study (GOG) LAP2, which included clinically early stage endometrial cancer patients randomized to laparotomy versus laparoscopy for surgical staging. Patients were divided into risk groups based on criteria defined by GOG protocol 99. Differences in outcomes and adjuvant therapy were assessed within these risk groups. RESULTS: LAP2 included 715 patients 70 years or older. With increasing age, worse tumor characteristics were seen. Older patients received similar rates of adjuvant therapy when stratified by stage. Patients 70 years or older had significantly worse progression-free survival and overall survival, and on multivariate analysis, older age and high-risk uterine factors were predictors of progression-free survival and overall survival, whereas stage and lymph node metastases were not. When patients were divided into GOG protocol 99 risk categories, most of those who met the high-intermediate risk criteria did so based on age above 70 years and grade 2 to 3 disease. These patients had low risk of recurrence (3.3%) compared with those who met the criteria by age above 70 years and all 3 uterine factors (20.9%). CONCLUSIONS: In early stage endometrial cancer, patients 70 years or older who undergo similar surgical management and adjuvant therapy, age and tumor characteristics independently predict recurrence. Most patients older than 70 years meet the high-intermediate risk criteria for recurrence based on age and 1 other uterine risk factor, and our results suggest that these patients are at low risk for recurrence.

Patterns and utility of routine surveillance in high grade endometrial cancer.

OBJECTIVE: To evaluate surveillance methods and their utility in detecting recurrence of disease in a high grade endometrial cancer population. METHODS: We performed a multi-institutional retrospective chart review of women diagnosed with high grade endometrial cancer between the years 2000 and 2011. Surveillance data was abstracted and analyzed. Surveillance method leading to detection of recurrence was identified and compared by stage of disease and site of recurrence. RESULTS: Two hundred and fifty-four patients met the criteria for inclusion. Vaginal cytology was performed in the majority of early stage patients, but was utilized less in advanced stage patients. CA-125 and CT imaging were used more frequently in advanced stage patients compared to early stage. Thirty-six percent of patients experienced a recurrence and the majority of initial recurrences (76%) had a distant component. Modalities that detected cancer recurrences were: symptoms (56%), physical exam (18%), surveillance CT (15%), CA-125 (10%), and vaginal cytology (1%). All local recurrences were detected by symptoms or physical exam findings. While the majority of loco-regional and distant recurrences (68%) were detected by symptoms or physical exam, 28% were detected by surveillance CT scan or CA 125. One loco-regional recurrence was identified by vaginal cytology but no recurrences with a distant component detected by this modality. CONCLUSIONS: Symptoms and physical examination identify the majority of high grade endometrial cancer recurrences, while vaginal cytology is the least likely surveillance modality to identify a recurrence. The role of CT and CA-125 surveillance outside of a clinical trial needs to be further reviewed.

Insulin exerts direct effects on carcinogenic transformation of human endometrial organotypic cultures.

Epidemiological studies suggest an association between elevated insulin levels and endometrial cancer. We studied the effects of insulin on normal endometrial cell proliferation with cytotoxicity assays. Organotypic cultures were used to determine the effects of insulin on the development of malignant histological features and anchorage independent growth. Western Blots were used to analyze the mitogen-activated protein kinases and AKT pathways. We found that insulin exerts direct effects on endometrial cells by increasing proliferation and promoting carcinogenesis. Our results suggest that this occurs through ERK 1/2 and glycogen synthase kinase-3ß Ser9 phosphorylation.

Referrals to phase I clinical trials in a gynecologic oncology unit.

OBJECTIVES: Previous reviews of phase I clinical trials report limited response rates. Development of novel biologic agents and trials designs have increased these rates. A contemporary appraisal of phase I clinical trials in gynecologic malignancies could help validate these findings. METHODS: Retrospectively reviewed records for 410 patients with gynecologic malignancies treated in a phase I unit, January 1999 to October 2012. Patient characteristics and treatment outcomes were abstracted and analyzed. RESULTS: Patients enrolled in 43 different phase I trials, 17 phase Ia, 17 phase Ib dose escalation and 9 dose expansion. 9 trials (21%) investigated unique cytotoxic delivery methods, 15 (35%) conventional cytotoxic plus novel agents and 19 (44%) novel agents alone. For patients treated in the first-line setting, 90 (74.4%) achieved CR, 20 (16.5%) PR, 9 (7.4%) SD and 2 (1.7%) PD, yielding an overall response rate of 90.9%. In patients treated for recurrent disease, 2 (1.6%) achieved CR, 11 (8.9%) PR, 57 (46.0%) SD and 54 (43.5%) PD, yielding a response rate of 11% and an overall clinical benefit rate of 57%. Response rate for molecular targeted therapies was 11.5% with an overall clinical benefit rate of 46.2%. Patients with prior anti-angiogenic exposure had comparable median PFS to those who had not been previously exposed (3.5 vs. 4.0 months, p = 0.29). CONCLUSIONS: Results support referral of gynecologic cancer patients for phase I clinical trials. Patients with advanced, heavily pretreated disease fare at least as well as they do on phase II trials and a proportion of them can attain an objective response or stabilization of their disease.

Carboplatin, paclitaxel, and pembrolizumab followed by pembrolizumab maintenance for primary treatment of incompletely resected epithelial ovarian cancer.

Objective: Incompletely resected epithelial ovarian cancer represents a poor prognostic subset of patients. Novel treatment strategies are needed to improve outcomes for this population. We evaluated a treatment strategy combining platinum-based chemotherapy with pembrolizumab followed by pembrolizumab maintenance therapy in the first-line treatment after incomplete resection of epithelial ovarian cancer patients. Methods: This was a single-arm, non-randomized pilot study of carboplatin, taxane, and immune checkpoint inhibitor, pembrolizumab, followed by 12 months of maintenance pembrolizumab in patients with incompletely resected epithelial ovarian cancer (EOC). Results: A total of 29 patients were enrolled and evaluated for efficacy and safety. The best response to therapy was complete response in 16 (55%) patients, partial response in 9 (31%) patients, and 3 (10%) patients with progression of disease. The median progression-free survival (PFS) was 13.2 months. Grade 3 and 4 toxicities occurred in 20% of patients. In all, 7 patients discontinued therapy due to adverse events. Quality-of-life scores remained high during therapy. Response to therapy did not correlate with PD-L1 tumor expression. Conclusions: Combination platinum-taxane therapy with pembrolizumab did not increase median progression-free survival in this cohort of patients. Key message: EOC is an immunogenic disease, but immune checkpoint inhibitor therapy has yet to impact outcomes. The current study utilized pembrolizumab in combination with standard chemotherapy followed by a maintenance treatment strategy in incompletely resected EOC. Progression-free survival was not extended in this poor prognostic group with combined chemotherapy and immunotherapy. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT 027766582.

Phase I and Randomized Phase II Study of Ruxolitinib With Frontline Neoadjuvant Therapy in Advanced Ovarian Cancer: An NRG Oncology Group Study.

PURPOSE: The interleukin-6/Janus kinase (JAK)/signal transducers and activators of transcription 3 axis is a reported driver of chemotherapy resistance. We hypothesized that adding the JAK1/2 inhibitor ruxolitinib to standard chemotherapy would be tolerable and improve progression-free survival (PFS) in patients with ovarian cancer in the upfront setting. MATERIALS AND METHODS: Patients with ovarian/fallopian tube/primary peritoneal carcinoma recommended for neoadjuvant chemotherapy were eligible. In phase I, treatment was initiated with dose-dense paclitaxel (P) 70 mg/m2 once daily on days 1, 8, and 15; carboplatin AUC 5 intravenously day 1; and ruxolitinib 15 mg orally (PO) twice a day, every 21 days (dose level 1). Interval debulking surgery (IDS) was required after cycle 3. Patients then received three additional cycles of chemotherapy/ruxolitinib, followed by maintenance ruxolitinib. In the randomized phase II, patients were randomly assigned to paclitaxel/carboplatin with or without ruxolitinib at 15 mg PO twice a day for three cycles, IDS, followed by another three cycles of chemotherapy/ruxolitinib, without further maintenance ruxolitinib. The primary phase II end point was PFS. RESULTS: Seventeen patients were enrolled in phase I. The maximum tolerated dose and recommended phase II dose were established to be dose level 1. One hundred thirty patients were enrolled in phase II with a median follow-up of 24 months. The regimen was well tolerated, with a trend toward higher grade 3 to 4 anemia (64% v 27%), grade 3 to 4 neutropenia (53% v 37%), and thromboembolic events (12.6% v 2.4%) in the experimental arm. In the randomized phase II, the median PFS in the reference arm was 11.6 versus 14.6 in the experimental, hazard ratio (HR) for PFS was 0.702 (log-rank P = .059). The overall survival HR was 0.785 (P = .24). CONCLUSION: Ruxolitinib 15 mg PO twice a day was well tolerated with acceptable toxicity in combination with paclitaxel/carboplatin chemotherapy. The primary end point of prolongation of PFS was achieved in the experimental arm, warranting further investigation.

Serum profiling to distinguish early- and late-stage ovarian cancer patients from disease-free individuals.

Sera mass spectrometry (MS) peak differences were analyzed from 35 ovarian cancer patients and 16 disease-free individuals. "Leave one out" cross validation was used to assign "% cancer peaks" in control and ovarian cancer sera samples. Sera MS discriminated stage I/II and stage III/V ovarian cancer patients versus controls with ROC curve area values of 0.82 and 0.92. Test sensitivities for ovarian cancer stage I/II and III/V were 80% and 93% respectively. These results indicate that MS is useful for distinguishing sera from early-stage ovarian cancer patients, and has potential as a test for early detection of this disease.

A case series of triplet anti-hormonal therapy in androgen receptor-positive recurrent adult ovarian granulosa cell tumor.

Therapeutic options for recurrent adult granulosa cell tumors (AGCT) are limited. After examining the hormonal pathways involved in FOXL2-mutated granulosa cell tumor development, a novel treatment regimen was utilized for recurrent AGCT: a combination of an androgen receptor antagonist, a gonadotropin-releasing hormone receptor agonist, and an aromatase inhibitor for hormonal blockade. In this case series, seven patients at our institution were treated with bicalutamide 50 mg orally once daily, Leuprolide acetate 7.5 mg intramuscular (IM) injection every 4 weeks, and a daily oral aromatase inhibitor. These patients had recurrent AGCT with androgen receptor positive tumors and had failed prior aromatase inhibitor therapy. All patients had undergone multiple surgical resections and many cycles of chemotherapy. Patients were monitored for toxicities and for response to treatment. Of the seven patients receiving the triple therapy, six saw clinical benefit. Two patients demonstrated a partial response and four patients had stable disease. One patient had progressive disease on the regimen. For the two patients who had a partial response to the triple therapy, there was strong expression of the androgen receptor (AR) noted on tumor immunohistochemistry. This drug combination was well-tolerated except for severe hot flashes in one patient. In conclusion, the triple therapy combination of an androgen receptor antagonist, aromatase inhibitor, and GnRH agonist demonstrated measurable responses in patients with recurrent AGCTs after multiple previous treatments. A prospective clinical trial is planned to further investigate these findings.

Same-Day Discharge After Robotic Hysterectomy: A Resource Utilization and Quality Improvement Project.

BACKGROUND: We implemented a low-cost education initiative to improve the rate of same-day discharge following hysterectomy performed for malignancy and assessed feasibility and impact on resource utilization. METHODS: Development and implementation of faculty, patient, clinical, and perioperative staff education regarding the goal of same-day discharge for patients undergoing robotic hysterectomy and staging by gynecologic oncologists was started in July 2019. Chart review of 103 patients prior to the intervention and 112 patients after the start of the intervention was completed. RESULTS: The rate of same-day discharge increased from 5% to 32% following the low-cost process change initiative, and a total of approximately 682 inpatient care hours were saved per 31 patients. DISCUSSION: The rate of same-day discharges after hysterectomy and staging performed by gynecologic oncologists can be safely increased with a simple educational intervention, which can save significant patient care resources.

Correction: Parashar et al. Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance. Cancers 2022, 14, 958.

The authors would like to correct the author byline to include Dr [...].

Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance.

Ovarian cancer is the most lethal gynecological malignancy among women worldwide and is characterized by aggressiveness, cancer stemness, and frequent relapse due to resistance to platinum-based therapy. Ovarian cancer cells metastasize through ascites fluid as 3D spheroids which are more resistant to apoptosis and chemotherapeutic agents. However, the precise mechanism as an oncogenic addiction that makes 3D spheroids resistant to apoptosis and chemotherapeutic agents is not understood. To study the signaling addiction mechanism that occurs during cancer progression in patients, we developed an endometrioid subtype ovarian cancer cell line named 'MCW-OV-SL-3' from the ovary of a 70-year-old patient with stage 1A endometrioid adenocarcinoma of the ovary. We found that the cell line MCW-OV-SL-3 exhibits interstitial duplication of 1q (q21-q42), where this duplication resulted in high expression of the PIK3C2B gene and aberrant activation of PI3K-AKT-ERK signaling. Using short tandem repeat (STR) analysis, we demonstrated that the cell line exhibits a unique genetic identity compared to existing ovarian cancer cell lines. Notably, the MCW-OV-SL-3 cell line was able to form 3D spheroids spontaneously, which is an inherent property of tumor cells when plated on cell culture dishes. Importantly, the tumor spheroids derived from the MCW-OV-SL-3 cell line expressed high levels of c-Kit, PROM1, ZEB1, SNAI, VIM, and Twist1 compared to 2D monolayer cells. We also observed that the hyperactivation of ERK and PI3K/AKT signaling in these cancer cells resulted in resistance to cisplatin. In summary, the MCW-OV-SL3 endometrioid cell line is an excellent model to study the mechanism of cancer stemness and chemoresistance in endometrioid ovarian cancer.

The expression of hepatocyte growth factor (HGF) and c-Met in uterine serous carcinoma.

OBJECTIVE: The hepatocyte growth factor (HGF) receptor c-Met plays an important role in tumor dissemination by activating mitogenic signaling pathways. The goal of this study was to investigate immunohistochemical (IHC) staining patterns of HGF and c-Met in endometrioid endometrial cancer (EC) and uterine serous cancer (USC) and to correlate staining with patient outcomes. METHODS: A tissue microarray was created using tissue from patients with atrophic endometrium (AE), grade 1 EC, grade 3 EC, and USC. Immunohistochemistry was used to detect c-Met, phosphorylated c-Met (p-c-Met), and HGF expression. Differences between IHC staining intensity were calculated using t-tests. Correlations between staining and clinicopathologic variables were determined by Chi-square testing for categorical variables and t-tests for continuous variables. Kaplan-Meier curves were constructed to analyze survival in USC. RESULTS: Patients with cancer had more total c-Met and HGF expression than those with AE (p=0.037, p<0.001 respectively), but no difference in p-c-Met staining. Total c-Met and HGF staining was significantly different between groups (p=0.042, p<0.001 respectively). This difference was accounted for by greater c-MET expression in USC compared to AE (p=0.027). Depth of invasion, stage, and lymph node status were not significantly related to staining intensity. Patients with strong c-Met and HGF staining had decreased overall survival compared to patients with weaker staining. CONCLUSIONS: HGF and c-Met may play a role in the progression of endometrial cancer and should be studied further as prognostic and therapeutic tools.

Acute cardiopulmonary failure in a young woman with high-risk gestational trophoblastic neoplasia: A case of induction chemotherapy during extracorporeal membrane oxygenation.

•Early use of extracorporeal membrane oxygenation (ECMO) is valuable when pulmonary tumor burden from GTN is high.•Induction chemotherapy of cisplatin and etoposide was administered during ECMO successfully.•The induction chemotherapy regimen led to exponential decline in beta-HCG after 1 cycle.•Collaboration of subspecialists is necessary to treat coexisting malignancy and cardiopulmonary failure associated with GTN.

Targeted biologic inhibition of both tumor cell-intrinsic and intercellular CLPTM1L/CRR9-mediated chemotherapeutic drug resistance.

Recurrence of therapy-resistant tumors is a principal problem in solid tumor oncology, particularly in ovarian cancer. Despite common complete responses to first line, platinum-based therapies, most women with ovarian cancer recur, and eventually, nearly all with recurrent disease develop platinum resistance. Likewise, both intrinsic and acquired resistance contribute to the dismal prognosis of pancreatic cancer. Our previous work and that of others has established CLPTM1L (cleft lip and palate transmembrane protein 1-like)/CRR9 (cisplatin resistance related protein 9) as a cytoprotective oncofetal protein that is present on the tumor cell surface. We show that CLPTM1L is broadly overexpressed and accumulated on the plasma membrane of ovarian tumor cells, while weakly or not expressed in normal tissues. High expression of CLPTM1L is associated with poor outcome in ovarian serous adenocarcinoma. Robust re-sensitization of resistant ovarian cancer cells to platinum-based therapy was achieved using human monoclonal biologics inhibiting CLPTM1L in both orthotopic isografts and patient-derived cisplatin resistant xenograft models. Furthermore, we demonstrate that in addition to cell-autonomous cytoprotection by CLPTM1L, extracellular CLPTM1L confers resistance to chemotherapeutic killing in an ectodomain-dependent fashion, and that this intercellular resistance mechanism is inhibited by anti-CLPTM1L biologics. Specifically, exosomal CLPTM1L from cisplatin-resistant ovarian carcinoma cell lines conferred resistance to cisplatin in drug-sensitive parental cell lines. CLPTM1L is present in extracellular vesicle fractions of tumor culture supernatants and in patients' serum with increasing abundance upon chemotherapy treatment. These findings have encouraging implications for the use of anti-CLPTM1L targeted biologics in the treatment of therapy-resistant tumors.