Mucinous, endometrioid, and serous ovarian cancers with peritoneal dissemination are potent candidates for P-cadherin targeted therapy: a retrospective cohort study

Abstract Background Aberrant expression of P-cadherin has been reported in various cancers, and has been attracting attention as a target for cancer treatment. Ovarian cancer, the leading cause of death among gynecologic malignancies, is classified into four histological subtypes: serous, mucinous, endometrioid, and clear cell, and each has distinct biological behavior. Although a negative survival impact in serous ovarian cancer patients and some functional role in peritoneal dissemination have been reported, differences of P-cadherin expression in histological subtypes and the proportion and distribution of positive cells remain to be investigated. The aims of this study were to clarify the histological and distributional profiles of P-cadherin expression in ovarian cancer for development of target-therapy in near future. Methods A total of 162 primary, 60 metastatic, and 8 recurrent tumors (all cases from 162 ovarian cancer patients) were enrolled in the study. Immunohistochemistry was performed for P-cadherin expression. Associations with clinicopathological characteristics and survival were analyzed. Results P-cadherin expression showed a strong correlation with the FIGO stage, histological subtypes, positive peritoneal dissemination (P < 0.01), positive distant metastasis (P < 0.05), and trend toward negative overall survival probability (P = 0.050). P-cadherin was intensely and broadly expressed in mucinous, endometrioid, and serous subtypes (P < 0.01). Disseminated tumors demonstrated similar P-cadherin expression to primary tumors whereas metastatic lymph nodes demonstrated significantly decreased expression (P < 0.01). Conclusions Mucinous, endometrioid, and serous ovarian cancer patients accompanied with peritoneal disseminations are the most potent candidates for P-cadherin targeted drug delivery strategies. P-cadherin-targeted therapy may benefit and improve survival of poor-prognosis populations.

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SHOULD AROMATASE INHIBITORS BE USED AS MAINTENANCE TREATMENT IN HIGH-GRADE SEROUS OVARIAN CANCER PATIENTS?

10.26226/morressier.599bdc7ad462b80296ca1822 ◽

2017 ◽

Author(s):

Alexandra Maria Knipprath-Mészáros

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Aromatase Inhibitors ◽

Maintenance Treatment ◽

High Grade ◽

Serous Ovarian Cancer

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Molecular predictors of the outcome of paclitaxel plus carboplatin neoadjuvant therapy in high-grade serous ovarian cancer patients

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-021-04301-6 ◽

2021 ◽

Author(s):

Anna P. Sokolenko ◽

Tatiana V. Gorodnova ◽

Ilya V. Bizin ◽

Ekaterina Sh. Kuligina ◽

Khristina B. Kotiv ◽

...

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

High Grade ◽

Serous Ovarian Cancer

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Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China

BMC Cancer ◽

10.1186/s12885-021-07946-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ruofei Du ◽

Xin Wang ◽

Lixia Ma ◽

Leon M. Larcher ◽

Han Tang ◽

...

Keyword(s):

Targeted Therapy ◽

Cancer Patients ◽

Adverse Reactions ◽

Cox Regression ◽

Target Therapy ◽

Skin Damage ◽

Data Set ◽

Patients With Cancer ◽

Number Of Patients ◽

Significant Difference

Abstract Background The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data. Methods A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups. Results A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group. Conclusion The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.

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Roles of E-cadherin and Cyclooxygenase Enzymes in Predicting Different Survival Patterns of Optimally Cytoreduced Serous Ovarian Cancer Patients

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2012.13.11.5715 ◽

2012 ◽

Vol 13 (11) ◽

pp. 5715-5719 ◽

Cited By ~ 8

Author(s):

Salih Taskin ◽

Ilkkan Dunder ◽

Ebru Erol ◽

Elif Aylin Taskin ◽

Saba Kiremitci ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Serous Ovarian Cancer ◽

Survival Patterns ◽

E Cadherin

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Knowledge and Anxiety Related to Hereditary Ovarian Cancer in Serous Ovarian Cancer Patients

Korean Journal of Women Health Nursing ◽

10.4069/kjwhn.2019.25.4.365 ◽

2019 ◽

Vol 25 (4) ◽

pp. 365 ◽

Cited By ~ 1

Author(s):

Sang Hee Lee ◽

Hyangkyu Lee ◽

Myong Cheol Lim ◽

Sue Kim

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Serous Ovarian Cancer ◽

Hereditary Ovarian Cancer

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Classification of serous ovarian cancer patients with suboptimal surgical outcomes by clinical molecular features

Gynecologic Oncology ◽

10.1016/j.ygyno.2018.04.407 ◽

2018 ◽

Vol 149 ◽

pp. 179

Author(s):

A.M. Newtson ◽

M.E. McDonald ◽

H.D. Reyes ◽

Y.A. Lyons ◽

M.J. Goodheart ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Surgical Outcomes ◽

Serous Ovarian Cancer ◽

Molecular Features

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Heterotypic CAF-tumor spheroids promote early peritoneal metastasis of ovarian cancer

Journal of Experimental Medicine ◽

10.1084/jem.20180765 ◽

2019 ◽

Vol 216 (3) ◽

pp. 688-703 ◽

Cited By ~ 30

Author(s):

Qinglei Gao ◽

Zongyuan Yang ◽

Sen Xu ◽

Xiaoting Li ◽

Xin Yang ◽

...

Keyword(s):

Ovarian Cancer ◽

Peritoneal Dissemination ◽

Tumor Stroma ◽

Stromal Fibroblast ◽

Low Grade ◽

Cancer Associated Fibroblasts ◽

Serous Ovarian Cancer ◽

Active Involvement ◽

Essential Components ◽

Metastatic Capacity

High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade serous ovarian cancer (LGSOC). Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin α5high (ITGA5high) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination. Intriguingly, fibroblasts inside MUs support ATC survival and guide their peritoneal invasion before becoming essential components of the tumor stroma in newly formed metastases. Cancer-associated fibroblasts (CAFs) recruit ITGA5high ATCs to form MUs, which further sustain ATC ITGA5 expression by EGF secretion. Notably, LGSOC is largely devoid of CAFs and the resultant MUs, which might explain its metastatic delay. These findings identify a specialized MU architecture that amplifies the tumor–stroma interaction and promotes transcoelomic metastasis in HGSOC, providing the basis for stromal fibroblast-oriented interventions in hampering OC peritoneal propagation.

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