scholarly journals Emerging molecular-targeted therapies—the challenging case of endometrial cancer

2015 ◽  
Vol 1 (1) ◽  
pp. 8
Author(s):  
Ines Vasconcelos
Keyword(s):  
Endometrial Cancer ◽  
Targeted Therapies ◽  
Progressive Disease ◽  
Advanced Disease ◽  
Treatment Options ◽  
Therapy Resistance ◽  
The United States ◽  
Genetic Alterations ◽  
Persistent Disease ◽  
Disease Identification

<p>Endometrial cancer newly affects an estimated 54,870 women in the United States, being responsible for an estimated 10,170 deaths in 2015. It has demonstrated to harbor a complex carcinogenesis process, with limited treatment options for advanced or persistent disease. Identification and targeting of genetic alterations that lead to progressive disease and therapy resistance is not only challenging, but also often does not correlate with a clinical benefit. Targeted maintenance therapies in endometrial cancer have been largely disappointing. Nonetheless, targeted personalized treatment should be the main goal of treatment of advanced disease in the future. Due to the high variety of drugs being tested in early clinical trials, it is hard to keep pace with the latest developments and ongoing trials. This review aims to summarize the latest published and ongoing trials on targeted therapies in endometrial cancer.</p>

scholarly journals Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late

2018 ◽  
Vol 19 (8) ◽  
pp. 2380 ◽  
Author(s):  
Michiel Remmerie ◽  
Veerle Janssens
Keyword(s):  
Clinical Trials ◽  
Endometrial Cancer ◽  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Genetic Alterations ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Type Ii

Type II endometrial carcinomas (ECs) are responsible for most endometrial cancer-related deaths due to their aggressive nature, late stage detection and high tolerance for standard therapies. However, there are no targeted therapies for type II ECs, and they are still treated the same way as the clinically indolent and easily treatable type I ECs. Therefore, type II ECs are in need of new treatment options. More recently, molecular analysis of endometrial cancer revealed phosphorylation-dependent oncogenic signalling in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways to be most frequently altered in type II ECs. Consequently, clinical trials tested pharmacologic kinase inhibitors targeting these pathways, although mostly with rather disappointing results. In this review, we highlight the most common genetic alterations in type II ECs. Additionally, we reason why most clinical trials for ECs using targeted kinase inhibitors had unsatisfying results and what should be changed in future clinical trial setups. Furthermore, we argue that, besides kinases, phosphatases should no longer be ignored in clinical trials, particularly in type II ECs, where the tumour suppressive phosphatase protein phosphatase type 2A (PP2A) is frequently mutated. Lastly, we discuss the therapeutic potential of targeting PP2A for (re)activation, possibly in combination with pharmacologic kinase inhibitors.

Endometrial Cancer: genetic, metabolic characteristics, therapeutic strategies and nanomedicine

2021 ◽  
Vol 28 ◽  
Author(s):  
Yuxuan Cai ◽  
Bei Wang ◽  
Wen Xu ◽  
Kai Liu ◽  
Yisong Gao ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Precancerous Lesions ◽  
Hypoxia Inducible Factor ◽  
The United States ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
Current Application ◽  
Female Population ◽  
Von Hippel Lindau ◽  
Metabolic Characteristics

Background: Endometrial cancer is the fourth most common malignancy in the female population worldwide. It was estimated that 65,620 new cases and 12,590 subsequent deaths occurred in 2020 in the United States. Patients with type II and advanced endometrial cancer do not respond well to the current treatments. Therefore, endometrial cancer should be better understood in order to develop more effective treatments. Objective: To provide an overview of genetic, metabolic characteristics, therapeutic strategies and current application of nanotechnology surrounding endometrial cancer. Method: Relevant articles were retrieved from Pubmed and were systematically reviewed. Results: Hypoxia-inducible factor-1 and Von Hippel-Lindau factor participated in oncogenesis and progression of endometrial cancer, and Nrf2 was associated with oncogenesis. Various genetic alterations were found in endometrial cancer. The examination of the abnormal X chromosome inactivation may help with the diagnosis of endometrial cancer and its precancerous lesions. Some absent tumor suppressor genes, activated oncogenes were revealed by the genetically modified mouse models. Disorders in glucose and lipid metabolism were found in endometrial cancer. Current therapeutic strategies focused on the HIF-1α pathway, the mTOR pathway as well as immunotherapy. Nanotechnology showed great potential in endometrial cancer’s early diagnosis, metastasis determination and treatment. Conclusion: Endometrial cancer has been understood in various aspects, but the underlying mechanisms still remain relatively unknown, which might be the source of novel diagnostic, prognostic and therapeutic targets. Nanomedicine in endometrial cancer is poorly studied, but the current researches showed great results in treating endometrial cancer. It needs further researching.

scholarly journals PHARMACOTHERAPY OF NON-SMALL CELL LUNG CANCER: A SHORT REVIEW

2018 ◽  
Vol 11 (3) ◽  
pp. 7
Author(s):  
Balaji O
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Advanced Disease ◽  
Growth Factor Receptor ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

 Lung cancer is a global health problem with non-small cell lung cancer (NSCLC) being the most common histopathological variant causing almost 28% deaths in the United States of America. Platinum compounds were the mainstay of treatment, and since past 10 years, various newer targeted therapies have come into play. Epidermal growth factor receptor and anaplastic lymphoma kinase mutations play a major role in the development of advanced disease. Hence, targeted therapies and immunotherapies will remain an integral part in the management of advanced disease. Hence, this review focuses on the newer drugs approved by Food and Drug Administration to treat NSCLC

scholarly journals Molecular Genetics of Relapsed Diffuse Large B-Cell Lymphoma: Insight into Mechanisms of Therapy Resistance

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3553
Author(s):  
Madeleine R. Berendsen ◽  
Wendy B. C. Stevens ◽  
Michiel van den Brand ◽  
J. Han van Krieken ◽  
Blanca Scheijen
Keyword(s):  
B Cell ◽  
Molecular Mechanisms ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
B Cell Lymphoma ◽  
Therapy Resistance ◽  
Genetic Alterations ◽  
Comprehensive Overview ◽  
Large B Cell Lymphoma ◽  
Large B Cell

The majority of patients with diffuse large B-cell lymphoma (DLBCL) can be treated successfully with a combination of chemotherapy and the monoclonal anti-CD20 antibody rituximab. Nonetheless, approximately one-third of the patients with DLBCL still experience relapse or refractory (R/R) disease after first-line immunochemotherapy. Whole-exome sequencing on large cohorts of primary DLBCL has revealed the mutational landscape of DLBCL, which has provided a framework to define novel prognostic subtypes in DLBCL. Several studies have investigated the genetic alterations specifically associated with R/R DLBCL, thereby uncovering molecular pathways linked to therapy resistance. Here, we summarize the current state of knowledge regarding the genetic alterations that are enriched in R/R DLBCL, and the corresponding pathways affected by these gene mutations. Furthermore, we elaborate on their potential role in mediating therapy resistance, also in connection with findings in other B-cell malignancies, and discuss alternative treatment options. Hence, this review provides a comprehensive overview on the gene lesions and molecular mechanisms underlying R/R DLBCL, which are considered valuable parameters to guide treatment.

Treatment patterns among patients with advanced/recurrent endometrial cancer in the United States.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 291-291
Author(s):  
Jinan Liu ◽  
Eric M Maiese ◽  
Bruno Émond ◽  
Marie-Hélène Lafeuille ◽  
Patrick Lefebvre ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Treatment Options ◽  
Patient Characteristics ◽  
The United States ◽  
Treatment Patterns ◽  
First Line ◽  
Kaplan Meier ◽  
The Us ◽  
Recurrent Endometrial Cancer ◽  
Third Line

291 Background: Among patients (pts) with endometrial cancer (EC), response rates for platinum-based regimens in the first-line (1L) setting range from 40% to 62% in clinical trials. This study describes patient characteristics, treatment patterns, time to next treatment (TTNT), and overall survival (OS) among pts with advanced/recurrent EC treated with a platinum-based regimen in a real-world setting in the US. Methods: This retrospective study used Optum Clinformatics Extended Data Mart de-identified databases from January 1, 2007, to December 31, 2019. Adult pts with advanced/recurrent EC who initiated a 1L platinum-based regimen and subsequently initiated second-line (2L) antineoplastic therapy were identified. Prior to initiation of 1L, a 12-month washout period of continuous enrollment without use of antineoplastic agents (except hormonal agents) was imposed. Kaplan-Meier (KM) rates were used to report TTNT and OS from 2L, third line (3L), and fourth line (4L), separately. Results: A total of 1878 pts with advanced/recurrent EC initiated 2L therapy following a platinum-based regimen in 1L. Among them, 739 (39.4%) pts initiated 3L and 330 (17.6%) initiated 4L or later (4L+) therapy. Median pt age was 68.0 years. More pts received platinum-based regimens (56.4%) in 2L than other options (Table). Few pts (3.3%) received immunotherapy. Among pts receiving 3L, a similar percentage of pts were treated with platinum-based (33.2%) and other chemotherapy regimens (33.8%); few pts received immunotherapy (3.0%). Among pts receiving 4L+, the most frequent treatment option was other chemotherapy (46.1%). Median TTNT was 17.7, 10.6, and 8.4 months for 2L, 3L, and 4L pts, respectively. KM rates of OS following initiation of 2L therapy at 1, 2, 3, and 4 years were 68.4%, 49.6%, 41.3%, and 33.6%, respectively, with a median OS of 23.5 months. Conclusions: Among pts with advanced/recurrent EC treated with platinum-based therapy in 1L, platinum-based regimens remain prevalent treatment choices in later lines of therapy. In this study, immunotherapy was used infrequently in 2L, 3L, and 4L+. The median TTNT decreased in later lines of therapy. This study highlights a critical need for novel, more effective treatment options in later lines of therapy to optimize outcomes among pts with advanced/recurrent EC.[Table: see text]

Treatment patterns among patients with advanced/recurrent endometrial cancer in the United States.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18693-e18693
Author(s):  
Eric M. Maiese ◽  
Bruno Émond ◽  
Jinan Liu ◽  
Marie-Hélène Lafeuille ◽  
Patrick Lefebvre ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Treatment Options ◽  
Patient Characteristics ◽  
The United States ◽  
Treatment Patterns ◽  
First Line ◽  
Kaplan Meier ◽  
The Us ◽  
Recurrent Endometrial Cancer ◽  
Third Line

e18693 Background: Among patients (pts) with endometrial cancer (EC), response rates for platinum-based regimens in the first-line (1L) setting range from 40% to 62% in clinical trials. This study describes patient characteristics, treatment patterns, time to next treatment (TTNT), and overall survival (OS) among pts with advanced/recurrent EC treated with a platinum-based regimen in a real-world setting in the US. Methods: This retrospective study used Optum Clinformatics Extended Data Mart de-identified databases from January 1, 2007, to December 31, 2019. Adult pts with advanced/recurrent EC who initiated a 1L platinum-based regimen and subsequently initiated second-line (2L) antineoplastic therapy were identified. Prior to initiation of 1L, a 12-month washout period of continuous enrollment without use of antineoplastic agents (except hormonal agents) was imposed. Kaplan-Meier (KM) rates were used to report TTNT and OS from 2L, third line (3L), and fourth line (4L), separately. Results: A total of 1878 pts with advanced/recurrent EC initiated 2L therapy following a platinum-based regimen in 1L. Among them, 739 (39.4%) pts initiated 3L and 330 (17.6%) initiated 4L or later (4L+) therapy. Median pt age was 68.0 years. More pts received platinum-based regimens (56.4%) in 2L than other options (Table). Few pts (3.3%) received immunotherapy. Among pts receiving 3L, a similar percentage of pts were treated with platinum-based (33.2%) and other chemotherapy regimens (33.8%); few pts received immunotherapy (3.0%). Among pts receiving 4L+, the most frequent treatment option was other chemotherapy (46.1%). Median TTNT was 17.7, 10.6, and 8.4 months for 2L, 3L, and 4L pts, respectively. KM rates of OS following initiation of 2L therapy at 1, 2, 3, and 4 years were 68.4%, 49.6%, 41.3%, and 33.6%, respectively, with a median OS of 23.5 months. Conclusions: Among pts with advanced/recurrent EC treated with platinum-based therapy in 1L, platinum-based regimens remain prevalent treatment choices in later lines of therapy. In this study, immunotherapy was used infrequently in 2L, 3L, and 4L+. The median TTNT decreased in later lines of therapy. This study highlights a critical need for novel, more effective treatment options in later lines of therapy to optimize outcomes among pts with advanced/recurrent EC.[Table: see text]

scholarly journals Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

2021 ◽  
Vol 19 (4) ◽  
pp. 439-457
Author(s):  
Margaret A. Tempero ◽  
Mokenge P. Malafa ◽  
Mahmoud Al-Hawary ◽  
Stephen W. Behrman ◽  
Al B. Benson ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Patient Outcomes ◽  
Advanced Disease ◽  
Treatment Options ◽  
Locally Advanced ◽  
Survival Rates ◽  
The United States ◽  
Nccn Guidelines

Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients’ advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.

scholarly journals Recent Advances in Endometrial Cancer

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 81 ◽  
Author(s):  
Arthur-Quan Tran ◽  
Paola Gehrig
Keyword(s):  
Endometrial Cancer ◽  
Genetic Basis ◽  
Advanced Disease ◽  
Early Stage ◽  
Molecular Targets ◽  
The United States ◽  
Gynecologic Malignancy ◽  
Early Stage Disease ◽  
Stage Disease ◽  
New Molecular Targets

Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer.

scholarly journals Bad Neighborhood: Fibrotic Stroma as a New Player in Melanoma Resistance to Targeted Therapies

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1364 ◽  
Author(s):  
Serena Diazzi ◽  
Sophie Tartare-Deckert ◽  
Marcel Deckert
Keyword(s):  
Protein Kinase ◽  
Targeted Therapies ◽  
Mapk Pathway ◽  
Therapy Resistance ◽  
Genetic Alterations ◽  
Mitogen Activated Protein Kinase ◽  
Driver Mutations ◽  
Melanoma Tumor ◽  
Inflammatory Microenvironment ◽  
Mitogen Activated Protein

Current treatments for metastatic cutaneous melanoma include immunotherapies and drugs targeting key molecules of the mitogen-activated protein kinase (MAPK) pathway, which is often activated by BRAF driver mutations. Overall responses from patients with metastatic BRAF mutant melanoma are better with therapies combining BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. However, most patients that initially respond to therapies develop drug resistance within months. Acquired resistance to targeted therapies can be due to additional genetic alterations in melanoma cells and to non-genetic events frequently associated with transcriptional reprogramming and a dedifferentiated cell state. In this second scenario, it is possible to identify pro-fibrotic responses induced by targeted therapies that contribute to the alteration of the melanoma tumor microenvironment. A close interrelationship between chronic fibrosis and cancer has been established for several malignancies including breast and pancreatic cancers. In this context, the contribution of fibrosis to drug adaptation and therapy resistance in melanoma is rapidly emerging. In this review, we summarize recent evidence underlining the hallmarks of fibrotic diseases in drug-exposed and resistant melanoma, including increased remodeling of the extracellular matrix, enhanced actin cytoskeleton plasticity, high sensitivity to mechanical cues, and the establishment of an inflammatory microenvironment. We also discuss several potential therapeutic options for manipulating this fibrotic-like response to combat drug-resistant and invasive melanoma.

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