scholarly journals Identification of KIF11 As a Novel Target in Meningioma

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 545 ◽  
Author(s):  
Jungwirth ◽  
Yu ◽  
Moustafa ◽  
Rapp ◽  
Warta ◽  
...  
Keyword(s):  
Functional Role ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Microarray Dataset ◽  
Who Grade ◽  
Meningioma Cell ◽  
New Treatment ◽  
Novel Target ◽  
Intracellular Vesicle Transport

Kinesins play an important role in many physiological functions including intracellular vesicle transport and mitosis. The emerging role of kinesins in different cancers led us to investigate the expression and functional role of kinesins in meningioma. Therefore, we re-analyzed our previous microarray dataset of benign, atypical, and anaplastic meningiomas (n = 62) and got evidence for differential expression of five kinesins (KIFC1, KIF4A, KIF11, KIF14 and KIF20A). Further validation in an extended study sample (n = 208) revealed a significant upregulation of these genes in WHO°I to °III meningiomas (WHO°I n = 61, WHO°II n = 88, and WHO°III n = 59), which was most pronounced in clinically more aggressive tumors of the same WHO grade. Immunohistochemical staining confirmed a WHO grade-associated upregulated protein expression in meningioma tissues. Furthermore, high mRNA expression levels of KIFC1, KIF11, KIF14 and KIF20A were associated with shorter progression-free survival. On a functional level, knockdown of kinesins in Ben-Men-1 cells and in the newly established anaplastic meningioma cell line NCH93 resulted in a significantly inhibited tumor cell proliferation upon siRNA-mediated downregulation of KIF11 in both cell lines by up to 95% and 71%, respectively. Taken together, in this study we were able to identify the prognostic and functional role of several kinesin family members of which KIF11 exhibits the most promising properties as a novel prognostic marker and therapeutic target, which may offer new treatment options for aggressive meningiomas.

scholarly journals Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 304
Author(s):  
Marta Araujo-Castro ◽  
Eider Pascual-Corrales ◽  
Javier Molina-Cerrillo ◽  
Teresa Alonso-Gordoa
Keyword(s):  
Adrenocortical Carcinoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Mechanisms Of Resistance ◽  
Response Efficacy ◽  
Predictors Of Response ◽  
Primary Endpoints ◽  
Tumor Mutational Burden

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.

scholarly journals PCV chemotherapy alone for WHO grade 2 oligodendroglioma: prolonged disease control with low risk of malignant progression

2021 ◽  
Author(s):  
Jonathan Weller ◽  
Sophie Katzendobler ◽  
Philipp Karschnia ◽  
Stefanie Lietke ◽  
Rupert Egensperger ◽  
...  
Keyword(s):  
Stereotactic Biopsy ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Who Grade ◽  
Free Survival ◽  
First Relapse ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
Histological Progression

Abstract Introduction The role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy. Methods Patients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy. Presurgical MRI T2 tumor volumes were obtained by manual segmentation. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of histological progression to grade 3 were analyzed. Results PFS was longest after PCV (9.1 years), compared to 5.1 years after W&S, 4.4 years after RES and 3.6 years after TMZ. The rate of histological progression from grade 2 to 3 within 10 years was 9% for the PCV, 29% for the W&S, 67% for the RES and 75% for the TMZ group (p = 0.01). In the W&S group, patients treated with PCV at first relapse had a longer PFS from intervention than those treated with TMZ (7.2 vs 4.0 years, p = 0.04). Multivariate analysis identified smaller tumor volume prior to any intervention (p = 0.02) to be prognostic for PFS. Conclusions PCV chemotherapy alone is an effective treatment for WHO grade 2 oligodendroglioma, with long PFS and low rate of histological progression.

scholarly journals Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

2021 ◽  
Vol 11 ◽  
Author(s):  
Codruţa Şoica ◽  
Mirela Voicu ◽  
Roxana Ghiulai ◽  
Cristina Dehelean ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Active Role ◽  
Structural Features ◽  
Sex Hormone ◽  
Ongoing Research ◽  
New Treatment ◽  
Highly Correlated

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

scholarly journals Role of Integrins in Resistance to Therapies Targeting Growth Factor Receptors in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 692 ◽  
Author(s):  
Elisabete Cruz da Silva ◽  
Monique Dontenwill ◽  
Laurence Choulier ◽  
Maxime Lehmann
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Treatment Options ◽  
Cancer Cell Proliferation ◽  
Remarkable Feature ◽  
Rtk Signaling ◽  
Intracellular Signal ◽  
New Treatment

Integrins contribute to cancer progression and aggressiveness by activating intracellular signal transduction pathways and transducing mechanical tension forces. Remarkably, these adhesion receptors share common signaling networks with receptor tyrosine kinases (RTKs) and support their oncogenic activity, thereby promoting cancer cell proliferation, survival and invasion. During the last decade, preclinical studies have revealed that integrins play an important role in resistance to therapies targeting RTKs and their downstream pathways. A remarkable feature of integrins is their wide-ranging interconnection with RTKs, which helps cancer cells to adapt and better survive therapeutic treatments. In this context, we should consider not only the integrins expressed in cancer cells but also those expressed in stromal cells, since these can mechanically increase the rigidity of the tumor microenvironment and confer resistance to treatment. This review presents some of these mechanisms and outlines new treatment options for improving the efficacy of therapies targeting RTK signaling.

scholarly journals Where does transplant fit in the age of targeted therapies?

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 287-293 ◽  
Author(s):  
Victor A. Chow ◽  
Ajay K. Gopal
Keyword(s):  
Follicular Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Low Toxicity ◽  
First Recurrence ◽  
Autologous Hct

Abstract The role of hematopoietic cell transplantation (HCT) for indolent lymphoma has evolved over the last 5 years with the availability of novel low-toxicity therapies and a better understanding of the prognosis of these entities. However, despite numerous treatment options for patients with follicular lymphoma, none are thought to be curative, and many require ongoing therapy with chronic toxicity. Historical trials indicate that autologous HCT as initial consolidation leads to improved progression-free survival, but not overall survival (OS) and, thus, is not typically recommended. However, autologous HCT for chemosensitive relapse can be carried out with ∼1% early mortality risk, affording disease control lasting a median of 3 to 5 years and the potential to improve OS. These results may compare favorably in efficacy, toxicity, and cost vs multiple sequential novel therapies with shorter durations of benefit. Recent data indicate that autologous HCT in follicular lymphoma patients with early initial progression will result in more than one third being alive and without relapse at 5 years, leading to improved OS when used within a year of the first recurrence. Unlike other available therapies, allogeneic HCT has the potential to cure up to one half of those transplanted with indolent B-cell non-Hodgkin lymphoma, although the risks need to be recognized and appropriate patient and donor selection is critical to ensure the best outcomes. HCT continues to remain a viable option in the current era of multiple targeted agents.

Comparative effectiveness research in renal cell carcinoma: Lenvatinib with everolimus as a potential new treatment option.

2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 27-27 ◽  
Author(s):  
Gabriel Tremblay ◽  
Corey Pelletier ◽  
Unnati Majethia ◽  
Anna Forsythe
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Comparative Effectiveness ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Treatment Comparison ◽  
Hazard Ratios ◽  
New Treatment ◽  
Comparative Effectiveness Analysis

27 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer and represents about 90% of all kidney cancers. As comprehensive comparison of the efficacy associated with mRCC treatments is not available, the goal of this research was to provide a comparative effectiveness analysis including overall survival (OS) and progression free survival (PFS) for first and second line treatments. Methods: Systematic literature review yielded the following randomized active-controlled studies: lenvatinib + everolimus (LEN+EVE) versus everolimus (EVE), axinitib (AXI) versus sorafenib (SOR), cabozantinib (CAB) versus EVE, nivolumab (NIV) versus EVE, and pazopanib (PAZ) versus sunitinib (SUN). In addition, placebo-controlled studies were identified for EVE, PAZ, and SOR. An indirect treatment comparison (ITC) was performed on OS and PFS hazard ratios (HR). Results: Scenario A presents the HR and confidence intervals (95% CI) generated with ITC of all treatments against EVE. In scenario B, the HR of LEN + EVE are compared to all treatment options. Only LEN + EVE and CAB demonstrated significance against EVE for both OS and PFS. LEN + EVE proved to be significant against EVE, PAZ, SOR, SUN, AXI and NIV for PFS and against EVE, SOR and AXI for OS. The use of crossover trials in the network for the treatment compared to placebo remains a potential bias in the results. Conclusions: Even if limitations exist regarding the use of ITC, the option of LEN+EVE demonstrated a strong comparative effectiveness profile for both OS and PFS. [Table: see text]

Biologic therapies in systemic lupus erythematosus

2016 ◽  
Author(s):  
Maria Mouyis ◽  
David Isenberg
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Treatment Options ◽  
Biologic Therapies ◽  
Systemic Lupus ◽  
New Treatment ◽  
Anti Cd20

This chapter looks at the various biologic or target therapies that have been trialled and tested in the last two decades. The treatment of systemic lupus erythematosus (SLE) has progressed over the last few years due to an increased understanding of its pathogenesis; beginning with rituximab, one of the first biologics to be used, the chapter covers therapies up to the present day. Each subsection highlights the relevant mechanism of action which has led to new treatment options: anti-CD20 and 22, anti-B cell activating factors, anti-interferon alpha and anti-T cell activation. A summarized table is available providing a concise summary of the latest biologic therapies in treating SLE. The role of biologic therapies as monotherapy is still being defined, and with time there will be further change in the treatments available and the approach to the treatment of SLE using biologic therapies.

Psilocybin-assisted therapy for depression: How do we advance the field?

2019 ◽  
Vol 54 (3) ◽  
pp. 225-231 ◽  
Author(s):  
Sally E Meikle ◽  
Paul Liknaitzky ◽  
Susan L Rossell ◽  
Margaret Ross ◽  
Nigel Strauss ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Potential Role ◽  
Treatment Options ◽  
Clinical Environment ◽  
Psychedelic Drugs ◽  
Key Issues ◽  
New Treatment ◽  
Potential Use

In the quest for new treatment options for depression, attention is being paid to the potential role of psychedelic drugs. Psilocybin is of particular interest given its mechanism of action, its benefits in early trials and its relatively low side effects burden. This viewpoint outlines a number of key issues that remain to be elucidated about its potential use in the clinical environment, including clarification of the profile of people most likely to benefit and those who might experience adverse effects, longer-term outcomes and the role of psychotherapeutic input alongside the drug itself. There are also opportunities to understand better, the neurobiology underpinning its effects.

Analysis of the costs of bevacizumab plus cisplatin and gemcitabine versus cetuximab plus vinorelbine and cisplatin in patients with advanced non-small cell lung cancer (NSCLC) in France: Results from a cost modelling study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17560-e17560
Author(s):  
C. Chouaid ◽  
A. Vergnenègre ◽  
V. Florentin ◽  
S. Walzer
Keyword(s):  
Advanced Nsclc ◽  
Transition Probabilities ◽  
Treatment Options ◽  
Indirect Comparison ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Cost Modelling ◽  
Humanized Monoclonal Antibody ◽  
New Treatment ◽  
Using Data

e17560 Background: New treatment options for advanced NSCLC can offer improved survival over standard chemotherapy (CT). Bevacizumab (BEV), a humanized monoclonal antibody (MAb) directed against VEGF when combined with CT increases overall survival (median 13.6 months in the AVAiL study) and progression-free survival (PFS) in patients with advanced NSCLC compared with CT alone. Cetuximab (CTX), an IgG1 MAb which targets the epidermal growth factor receptor, achieved a median survival of 11.3 months when combined with CT in the FLEX study; marketing authorization is anticipated during 2009. The aim of this study was to compare the costs of treating patients with BEV plus cisplatin and gemcitabine (BCG) versus CTX plus vinorelbine and cisplatin (CVC) in France. Methods: A Markov model was used to compare drug and administration costs associated with treating advanced NSCLC with either BCG or CVC. The model assumes patients move from non-progressive to progressed disease to death, according to transition probabilities derived from an indirect comparison of the efficacy of BCG and CVC in terms of PFS using data from the respective pivotal trials and appropriate indirect comparison methodology. Cost data were derived from local sources. Drug costs assumed CT was given for up to 6 cycles, that CTX was administered at an initial dose of 400 mg/m2 followed by 250 mg/m2 weekly until progression and that BEV was administered at 7.5 mg/kg every 3 weeks until progression. The model estimated average drug and administration costs per patient treated with either BCG or CVC. Results: The mean cost for BCG and CVC was €23849 and €35678 respectively, resulting in a saving of €11829 per patient for BCG. The acquisition of BEV was less costly than the acquisition of CTX (€15374 vs €23530) and, BCG acquisition and administration costs were lower than CTX's respectively, €19756 versus €24750 and €4093 versus €10928. Conclusions: Targeted therapy using BEV is less costly than CTX in France, and therefore, from a budget perspective offers the best value for money approach to improving outcomes in patients with advanced NSCLC. [Table: see text]

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