scholarly journals Resistance to chemotherapy and hormone therapy in endometrial cancer

2009 ◽  
Vol 16 (2) ◽  
pp. 363-380 ◽  
Author(s):  
Parvesh Chaudhry ◽  
Eric Asselin

Endometrial cancer is the most common gynecological malignancy in developed countries and represents the eighth leading cause of cancer related death in women. The growing incidence of endometrial cancer leads scientists and oncologists to identify effective preventive measures and also molecular markers for diagnosis and prognosis. Chemotherapy and hormone therapy is the mainstay treatment option for advanced and recurrent endometrial cancer and response to therapy is one of the most important factor which favors prognosis and overall survival. In recent years, there have been major advances in the treatment of patients with endometrial cancer. Despite advances made in the treatment of this cancer, the overall survival of patients has not significantly improved because considerable number of patients harbor tumor refractory to these therapies and the majority of the initially responsive tumors become refractory to treatments. Therefore, determination of sensitivity/resistance is becoming increasingly important for individualization of endometrial cancer therapy. The aim of this review is to present the existing knowledge about the molecular markers that could play a crucial role in determining resistance to chemo- and hormone therapy. Extensive literature search for the cell signaling pathways and factors responsible for chemoresistance have been performed and reviewed. Several recent studies suggest that deregulations in the apoptotic pathways (such as p53, Fas/FasL, Bcl-2 family proteins, inhibitor of apoptosis proteins), survival pathways (PI3K/AKT, MAPK), hormone receptor signaling pathways (progesterone receptor), Cyclooxygenase-2 and Her-2 are considered as key factors involved in the onset and maintenance of therapeutic resistance, suggesting that resistance is a multi-factorial phenomenon.

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Tamara Sequeiros ◽  
Marta García ◽  
Melania Montes ◽  
Mireia Oliván ◽  
Marina Rigau ◽  
...  

Prostate cancer (PCa) is the most frequently diagnosed type of cancer in developed countries. The decisive method of diagnosis is based on the results of biopsies, morphologically evaluated to determine the presence or absence of cancer. Although this approach leads to a confident diagnosis in most cases, it can be improved by using the molecular markers present in the tissue. Both miRNAs and proteins are considered excellent candidates for biomarkers in formalin-fixed paraffin-embedded (FFPE) tissues, due to their stability over long periods of time. In the last few years, a concerted effort has been made to develop the necessary tools for their reliable measurement in these types of samples. Furthermore, the use of these kinds of markers may also help in establishing tumor grade and aggressiveness, as well as predicting the possible outcomes in each particular case for the different treatments available. This would aid clinicians in the decision-making process. In this review, we attempt to summarize and discuss the potential use of microRNA and protein profiles in FFPE tissue samples as markers to better predict PCa diagnosis, progression, and response to therapy.


2021 ◽  
pp. 20201314
Author(s):  
Lucia Manganaro ◽  
Gabriele Maria Nicolino ◽  
Miriam Dolciami ◽  
Federica Martorana ◽  
Anastasios Stathis ◽  
...  

Radiomics is an emerging field of research that aims to find associations between quantitative information extracted from imaging examinations and clinical data to support the best clinical decision. In the last few years, some papers have been evaluating the role of radiomics in gynecological malignancies, mainly focusing on ovarian cancer. Nonetheless, cervical cancer is the most frequent gynecological malignancy in developing countries and endometrial cancer is the most common in western countries. The purpose of this narrative review is to give an overview of the latest published papers evaluating the role of radiomics in cervical and endometrial cancer, mostly evaluating association with tumor prognostic factors, with response to therapy and with prediction of recurrence and distant metastasis.


2015 ◽  
Vol 156 (36) ◽  
pp. 1460-1471 ◽  
Author(s):  
Emese Irma Ágoston ◽  
Zsolt Baranyai ◽  
Kristóf Dede ◽  
György Bodoky ◽  
Janina Kulka ◽  
...  

Introduction: Besides clinicopathological parameters, molecular markers can be very important, and further characterize colorectal carcinomas into chromosomally unstable, microsatellite instable and “CqG-island methylator phenotype” groups. Aim: To study the frequency of microsatellite instability using immunohistochemical evaluation of MLH1, MSH2, MSH6 and PMS2 proteins in colorectal carcinoma. Method: 122 colorectal carcinomas as well as in 69 paired liver metastases were evaluated. Additionally, prognostic and predictive potential of mismatch repair status was tested. Results: Microsatellite instable phenotype was identified in 11.5% (14/122) of the tumours. There were no differences regarding staining intensity of tumour regions. Mismatch repair status was discordant in primaries vs. metastases in 20.2%. There was no difference in progression free- and overall survival according to mismatch repair status. The mismatch repair status was not predictive for survival within systemic therapy regimen groups. Conclusions: The subgroups of colorectal carcinomas could be evaluated in a larger and homogenised patient cohort to predict prognosis and response to therapy. Orv. Hetil., 2015, 156(36), 1460–1471.


2020 ◽  
Author(s):  
Vincenzo Dario Mandato ◽  
Valentina Mastrofilippo ◽  
Andrea Palicelli ◽  
Monica SILVOTTI ◽  
Silvia Serra ◽  
...  

Abstract BackgroundEndometrial cancer is the most common gynaecological malignancy in developed countries. It is usually diagnosed at early-stage and presents a favourable prognosis. Conversely, advanced or recurrent disease result in low response to therapy and poor outcome. Most recurrences occur within two years postoperatively, typically in pelvic and para-aortic lymph nodes, vagina, peritoneum, and lungs; unusual localizations include abdominal organs/wall, bones, brain, muscle. Vulvar metastasis are indeed anecdotal probably because the different regional lymphatic drainage from corpus uterus. Here, we report a case of vulvar metastasis from an early endometrial cancer comprehensive staged by laparoscopy and reviewed the literature discussing the different mechanisms of vulvar metastasis pathogenesis and the prognosis.MethodsWe reported a case of vulvar metastasis from an early stage endometrial cancer. We also collected and analysed articles written in English regarding vulvar metastasis form endometrial cancer published between January 1966 and May 2020. PubMed was used as a database for this search. Clinical and pathological characteristics, treatments and outcomes were assessed.In total, 19 cases of vulvar metastasis from endometrial cancer were found. Patients had a mean age of 66 years and were mostly asymptomatic. Labium major was the most common and usually unique site of metastasis. Vulvar metastasis were mostly nodular/mass-like lesions occurred in patients treated mostly for endometrial cancer at early stage. Median time to vulvar metastasis was ten months. Most of the metastasis were treated with surgery or radiotherapy. One third of patients presented a subsequent recurrence on average 11 months later. 61.1% of patients died of disease and 70 median overall survival was 16 months.Vulvar metastasis can show different appearance, occurring as single or diffuse lesions on healthyor injured skin, in patients treated for both early- and advanced-stage endometrial cancers. Surgicalapproach seems not to influence the risk of subsequent metastasis, but tumor seeding and vaginalinjuries should be avoided. Whether isolated or associated with recurrence in other locations, vulvarmetastasis are characterized by severe prognosis despite radical treatment. Therefore, any suspectedvulvar lesion arisen during endometrial cancer follow-up should be biopsied, despite the vulva represents an unusual metastatic site.ConclusionsVulvar metastasis can show different appearance. Surgical approach seems not to influence the risk of subsequent metastasis. Vulvar metastasis are characterized by severe prognosis despite radical treatment. Therefore, any suspected vulvar lesion arisen during follow-up should be biopsied.


Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 115
Author(s):  
Petra Vinklerová ◽  
Petra Ovesná ◽  
Markéta Bednaříková ◽  
Luboš Minář ◽  
Michal Felsinger ◽  
...  

Background: Endometrial cancer is the most common gynecological malignancy in developed countries with no screening available. There is still a tendency to provide invasive bioptic verification in asymptomatic women with abnormal ultrasound findings to diagnose carcinoma in a preclinical phase; even though, it is not supported by European guidelines. Our goal was to determine DFS (disease-free survival), OS (overall survival), and DSS (disease-specific survival) differences between symptom-free and symptomatic (bleeding, or spotting) endometrial cancer patients with similar stage and tumor/clinical characteristics. Methods: All of our patients with endometrial cancer following surgical treatment between 2006 and 2019 were assessed, evaluating risk factors for recurrence and death while focusing on bleeding using univariable and multivariable analysis. Results: 625 patients meeting the inclusion criteria were divided into asymptomatic (n = 144, 23%) and symptomatic (n = 481, 77%) groups. The median follow-up was 3.6 years. Using univariable analysis, symptomatic patients had a three times higher risk of recurrence (HR 3.1 (95% Cl 1.24–7.77), p = 0.016). OS (HR 1.35 (0.84–2.19), p = 0.219) and DSS (HR 1.66 (0.64–4.28), p = 0.3) were slightly worse without reaching statistical significance. In our multivariable analysis, symptomatology was deemed completely insignificant in all monitored parameters (DFS: HR 2.03 (0.79–5.24), p = 0.144; OS: HR 0.72 (0.43–1.21), p = 0.216). Conclusions: The symptomatic endometrial cancer patients risk factor of earlier recurrence and death is insignificantly higher when compared with the asymptomatic cohort. However, multivariable analysis verifies that prognosis worsens with other clinically relevant parameters, not by symptomatology itself. In terms of survival outcome in EC patients, we recognized symptomatology as a non-significant marker for the patient’s prognosis.


Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 7
Author(s):  
Luka Roškar ◽  
Irena Roškar ◽  
Tea Lanišnik Rižner ◽  
Špela Smrkolj

Endometrial cancer (EC) is the most frequent gynecological malignancy in developed countries and requires a relatively invasive diagnostic evaluation and operative therapy as the primary therapeutic approach. Angiogenesis is one of the main processes needed for cancer growth and spread. The production of angiogenic factors (AFs) appears early in the process of carcinogenesis. The detection of AFs in plasma and tissue and a better understanding of the angiogenic properties of EC may contribute not only to earlier but also more specific diagnosis and consequently tailored and individual therapeutic approaches. AFs and their receptors also have high potential as binding sites for targeted cancer therapy. In this review, we discuss angiogenesis in EC and the characteristics of the AFs that most contribute to angiogenesis in EC. We also highlight therapeutic strategies that target angiogenesis as potential EC therapy.


2017 ◽  
pp. 132-138
Author(s):  
O.V. Paliychuk ◽  
◽  
L.Z. Polishchuk ◽  
Z.I. Rossokha ◽  
◽  
...  

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.


2017 ◽  
Vol 63 (6) ◽  
pp. 843-854
Author(s):  
Olga Novikova ◽  
Yelena Ulrikh ◽  
V. Nosov ◽  
A. Charkhifalakyan

There is presented the review of domestic and foreign references on the conserved oncological safety of the use of menopausal hormone therapy after treatment for endometrial cancer, cervical cancer, borderline and malignant ovarian tumors, various variants of sarcomas of the uterus, vulva and vaginal cancer. To the opinion of the authors the refusal to prescribe menopausal hormone therapy to patients with oncogynecologic diseases in the anamnesis is usually not justified, the category of patients, to whom hormone replacement therapy is contraindicated, is well described and mentioned in the text. In other cases sex hormones can be used to treat menopausal symptoms and improve the quality of life of patients.


2020 ◽  
Vol 23 (1) ◽  
Author(s):  
Linas Andreika ◽  
Margarita Montrimaitė ◽  
Juliana Andreičik

Summary. Endometrial cancer is the most common gynecological cancer in developed countries. Biopsy of the sentinel lymph node can be considered as an alternative to full lymphadenectomy. In order to identify sentinel lymph nodes, a tracer substance is injected into the uterus to visualize the lymphatic tract. Commonly used tracer substances are Technetium-99m (99mTc) colloid, blue dyes, and indocyanine green (ICG). In this review the significance of sentinel lymph node biopsy in endometrial cancer management and the technique of the procedure is discussed.


2020 ◽  
Author(s):  
Soulaimane Aboulouard ◽  
Maxence Wisztorski ◽  
Marie Duhamel ◽  
Philippe Saudemont ◽  
Tristan Cardon ◽  
...  

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