Abstracts Ahead of Print | Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Lung Cancer

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Author(s): Alessandra Bearz, Sara Cecco, Sara Francescon, Francesco Lo Re, Giuseppe Corona, Paolo Baldo*.

 

 

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Background: Lung cancer is the most frequent cause of cancer-related death. In the last decades, the introduction of targeted therapies and more recently, of immunotherapy, has led to significant improvements in different outcomes of this malignant neoplasm.

Objective: The present review provides a balanced overview of most recent targeted therapies and immunotherapies patented for the treatment of lung cancer.

Method: An extensive scientific literature and patent databases search were performed to identify peer-reviewed studies containing information on recently patented drugs for the treatment of lung cancer, with a particular focus on their safety data and recently patented combinations.

Results: The development of therapies directed to different pathways involved in the tumor angiogenesis, proliferation, and metastasis has transformed the clinical practice of lung malignancies. Several clinical trials have shown an improvement in terms of progression-free survival and overall survival in patients with advanced/metastatic lung cancer. Safety data, extracted from clinical trials and from the WHO global database of adverse drug reactions (VigiAccessTM database), show that recently patented drugs for the treatment of lung cancer are well- tolerated and most of the adverse events reported are mild to moderate.

Conclusion: Currently, a consistent number of new drugs and combinations have been introduced for the treatment of patients with advanced-stage lung cancer. Safety data remain essential to better assess the long-term risk/benefit ratio of these valuable emerging therapies. The new patents’ development could provide further significant improvements for lung cancer treatment. To read full abstract, please visit: http://www.eurekaselect.com/173895/article

Abstracts Ahead of Print | Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Cutaneous Melanoma

Author(s): Debora Basile, Camilla Lisanti, Maria A. Pizzichetta, Paolo Baldo*, Giulia Fornasier, Francesco Lo Re, Giuseppe Corona, Fabio Puglisi.

 

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Background: Malignant melanoma is a skin cancer responsible of 90% of cutaneous cancer related deaths. In recent years, breakthroughs in treatment strategy have revolutionized the prognosis both of early and advanced melanoma patients. In particular, treatment with monoclonal antibodies targeting co-inhibitory checkpoints or specific molecular pathways are pawing the way for a new era of promising options, by prolonging survival time of these patients.

Moreover, unlike the chemotherapy that was used until some time ago, these new drugs have a good and more manageable toxicity profile. However, because of the recent introduction in clinical practice of the new agents, there is a learning curve among physicians regarding early recognition and management of the associated side effects.

Objectives: The analysis of the toxicity profiles of the different agents currently studied for the treatment of early and advanced melanoma, and the description of several relevant recent patents in this field, are the aims of this review.

Methods: A systematically conducted review, based on current clinical guidelines and on international Pharmacovigilance databases (AERS-Eudravigilance – WHO Vigibase).

Results: Our systematic analysis outlines a comprehensive overview about the pharmacology, clinical application and safety of recent anticancer drugs to treat melanoma, which can be an essential instrument for health professionals and researchers.

Conclusion: The new oncological therapies against melanoma are based on increasingly specific biological and immunological targets. For this reason, the potential toxicities that are expected from patients would be less relevant than the systemic “classical” chemotherapy. However, the new therapies are not free from the risk of causing adverse reactions, some of which must be managed promptly and appropriately; moreover the multiplicity of the metabolic pathways exposes the new target therapies to relevant potential interactions. This review can help to understand how important it is not to underestimate potential adverse drug reactions related to new targeted therapies. To read the full abstract, please visit: http://www.eurekaselect.com/173896/article

Abstracts Ahead of Print | Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Advanced Thyroid Cancer

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Author(s): Emanuela Vaccher, Ornella Schioppa, Ferdinando Martellotta, Giulia Fornasier, Elisa Giacomin, Francesco Lo Re, Paolo Baldo*, Giuseppe Corona, Carlo Gobitti.

 

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Background: Thyroid cancer is the most common endocrine neoplasia and represents approximately 1.5% to 2.1% of all cancers diagnosed annually worldwide. Iodine refractory differentiated thyroid carcinoma (RR-DTC) and advanced/metastatic medullary thyroid carcinoma are relatively uncommon yet prognostically significant thyroid cancers. Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers, including thyroid cancer. Many Multi-Kinase Inhibitors (MKIs) which are now FDA-/EMA-approved for thyroid cancer have shown clinical benefit in patients with advanced cancer. Treatment-related toxicities occur frequently with these drugs and can be severe or life-threatening.

Objectives: This review summarizes the role of targeted therapy with MKIs in the management of RR-DTC and advanced/metastatic MTC patients, focusing on side-effect profiles of these drugs, with a presentation of several recent patents published in this field.

Methods: We review the scientific literature about advanced thyroid cancer and we analyze the International Pharmacovigilance database (FAERS, Eudravigilance, and WHO Vigibase) for adverse drug reactions.

Results: This systematic analysis highlights the difference of the safety profile between the recent drugs used in the treatment of advanced thyroid cancer and the recent patient discovered to diagnose or to treat the thyroid cancer.

Conclusion: It is essential to investigate the safety profile of the recent anticancer drugs for advanced thyroid cancer to allow health professionals to make the best choice for each patient by evaluating the risk/benefit assessment. To read the full asbtract, please visit: http://www.eurekaselect.com/173897/article

Press Release | Estrogen is a much more effective anticancer agent than antiestrogens

 

This article by Prof. Zsuzsanna Suba is published in Recent Patents on Anti-Cancer Drug Discovery, Volume 12, Issue 2, 2017

Antiestrogen treatment was introduced into breast cancer therapy based on the presumed carcinogenic capacity of endogenous estrogen hormones. In antiestrogen resistant breast cancers, increased expression and activity of estrogen receptors (ERs) is regarded as a survival technique, presuming that increased estrogen signaling is an absolutely proliferative stimulus. Unexpectedly, among certain circumstances, estrogen treatment is capable of inducing apoptotic death in tumors, even in antiestrogen resistant ones justifying the strong apoptotic capacity of estrogen. Analysis of the results of studies on both estrogen and antiestrogen treated tumors may clarify the associations among artificial ER blockade, compensatory restoration of ER signaling and the clinical behavior of cancers.

Inherited BRCA1/2 mutations may be regarded as pathologic models of defective estrogen signaling. In BRCA mutation carriers, the liganded activation of ERs is weak, while an increase in unliganded ER activation results in a more or less compensatory upregulation of ER signaling. Mutation carriers exhibit failure in their ovarian functions, while their risk for cancer is strongly increased (for breast cancer in particular). In cases carrying BRCA mutation, an increase in estrogen levels via either endogenous estrogen synthesis in pregnancy or exogenous estrogen administration via contraceptive use may reduce the risk of cancer development.

Estrogen activated ERs are the principal initiators and organizers of DNA stabilization. ERs work in an upregulative circuit with CYP19 aromatase enzyme and genome safeguarding proteins including BRCAs. The upregulative circuit ensures a strong DNA protection during the proliferation of healthy cells, whilst inducing apoptotic death in spontaneously initiated malignant cells in a Janus faced manner. By contrast, malignant cell proliferation exhibits a downregulative circuit between the low and/or defective expressions of ER and BRCA proteins. The malfunction of ER signaling is coupled with a damaged control of DNA replication resulting in an unrestrained proliferation of poorly differentiated tumor cells. In conclusion, in patients with cancer, estradiol induced upregulation of ER signaling may be an excellent means for the restoration of genome stabilizer machinery and for inducing apoptotic death in cancer cells.

Estrogen treatment upregulates the remnants of genome stabilizer machinery in breast cancer cell lines so as to induce an apoptotic death. Estrogen administration increases the expression and transcriptional activity of ERs in tumor cells, via both liganded and unliganded pathways. In patients, of all examined tumor markers, an increased expression of ERs in their breast cancer defines the prolonged survival. Moreover, the activation of ER-alpha at Ser 167 in tumors is indicative of longer disease free and overall survival in breast cancer patients.

Estrogen treatment induces ESR1 gene amplification resulting in higher expression levels of ERs in breast cancers. Patients exhibiting ESR1 gene amplification in their tumors, experience longer disease free survival than those without it.

Estradiol treatment mediates an increased expression of long non coding RNAs (lncRNAs) including HOTAIR in breast cancer cells. HOTAIR is capable of epigenetic gene modifications resulting in necessary activating mutations in the ESR1 gene. Patients with increased HOTAIR expression in their tumors were found to have lower risks for relapse and mortality than those showing low HOTAIR expression.

Estradiol treatment increases aromatase expression and activity in breast cancer cells in a dose dependent manner. Estradiol activated ERs strongly upregulate the estrogen synthesis of aromatase enzyme so as to increase estrogen signaling and to induce consequential DNA restoration and apoptotic death. Among breast cancer cases, a direct correlation was experienced between the aromatase activity of removed tumors and the patient’s survival time after surgery. Moreover, among young women with breast cancer, the absence of CYP19 aromatase activity in their surgically removed tumors carried a high risk for local cancer recurrence.

Estrogen treatment induces an upregulated expression of DNA safeguarding BRCA1 protein in breast cancer cell lines. In turn, it was found that the BRCA1 protein promotes ESR1 gene activation and transcriptionally upregulates ER-alpha expression in tumor cells. These correlations justify that ER-alpha and BRCA1 protein work in close partnership in the DNA stabilization process which provides apoptotic stimuli for breast cancer cells.

In conclusion, treatment with estrogen may strongly upregulate both estrogen signaling and DNA safeguarding in breast cancers promoting tumor responses. In antiestrogen responsive tumors, the blockade of liganded ER activation via either tamoxifen or aromatase inhibitor, provokes compensatory overexpression and hyperactivity of both ERs and aromatase enzyme via unliganded activations of partially blocked ERs. This compensatory activation of estrogen signaling may restore DNA stability promoting tumor responses. By contrast, in antiestrogen resistant tumors, a long term, exhaustive tamoxifen or aromatase inhibitor treatment induces a compensatory extreme upregulation of ER signaling; however, it may be insufficient to break through the near complete, artificially induced ER blockade. Antiestrogen resistant tumors exhibit a rapid growth in spite of the continuous administration of antiestrogens.

 

Browse the Article at: Activating Mutations of ESR1, BRCA1 and CYP19 Aromatase Genes Confer Tumor Response in Breast Cancers Treated with Antiestrogens

EDITORS CHOICE ARTICLE – PARP Inhibitors in Ovarian Cancer

Journal Name: Recent Patents on Anti-Cancer Drug Discovery 

Author(s): Gloria Mittica, Eleonora Ghisoni, Gaia Giannone, Sofia Genta, Massimo Aglietta, Anna Sapino, Giorgio Valabrega*.

 

 

Abstract:

Background: Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients.

Objectives: The study aimed to highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis.

Methods: We performed a review on Pubmed using ‘ovarian cancer’ and the name of each PARPi (PARP inhibitor) discussed in the review as Medical Subject Headings (MeSH) keywords. The same search was performed on “clinicaltrial.gov” to identify ongoing clinical trials and on “google. com/patents” and “uspto.gov” for recent patents exploring PARPIs in ovarian cancer.

Results: Olaparib, Niraparib and Rucaparib are already approved for the treatment of recurrent EOC and their indications are partially overlapping. Talazoparib and Veliparib are promising PARPis, but currently under investigation in early phase trials. Several studies are evaluating PARPis in monotherapy or in associations, in a wide range of settings (i.e. first line, neoadjuvant, platinum-sensitive and resistant disease).

Conclusion: PARPis are valuable options in patients with recurrent ovarian cancer with promising activity in different stages of this disease. Further studies are required to better define optimal clinical settings, predictors of response beyond BRCA mutations and strategies to overcome secondary resistance of PARPis therapy in EOC.

 

For more details, please visit: http://www.eurekaselect.com/160235/article

New Issue :: Recent Patents on Anti-Cancer Drug Discovery (Volume: 13, Issue: 3)

 

Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.

 

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Articles from the journal Recent Patents on Anti-Cancer Drug Discovery Volume 13, Issue 3:

 

For details on the articles, please visit this link ::  https://bit.ly/2vquNfV

AIMS & SCOPE – Recent Patents on Anti-Cancer Drug Discovery

Aims & Scope:

Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.

 

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FOR DETAILS, PLEASE VISIT: https://benthamscience.com/journals/recent-patents-on-anti-cancer-drug-discovery/aims-scope/#top

MOST ACCESSED ARTICLE – Use of human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors in Autoimmune Diseases and New Perspectives in Cancer Therapy

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Author(s): Marco L. Lolli, Stefano Sainas, Agnese C. Pippione, Marta Giorgis, Donatella Boschi, Franco Dosio*.

 

 

 

Abstract:

Background: Human dihydroorotate dehydrogenase (hDHODH, EC 1.3.5.2), a flavindependent mitochondrial enzyme involved in de novo pyrimidine biosynthesis, is a validated therapeutic target for the treatment of autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis. However, human DHODH inhibitors have also been investigated as treatment for cancer, parasite infections (i.e. malaria) and viruses as well as in the agrochemicals industry.

Objective: An overview of current knowledge of hDHODH inhibitors and their potential uses in diseases where hDHODH is involved.

Method: This review focuses on recent advances in the development and application of hDHODH inhibitors, specifically covering the patent field, starting from a brief description of enzyme topography and of the strategies usually followed in designing its selective inhibitors.

Results: The most important and well-described novelty is the fact that the discovery, in the autumn of 2016, that hDHODH inhibitors are able to induce in vivo myeloid differentiation has led to the possibility of developing novel hDHODH based treatments for Acute Myelogenous Leukemia (AML).

Conclusion: The review will describe a variety of specific inhibitor classes and conclude on recent and future therapeutic perspectives for this target.

 

READ MORE HERE: http://www.eurekaselect.com/156928

OPEN ACCESS ARTICLE – Anaplastic Lymphoma Kinase in Glioblastoma: Detection/Diagnostic Methods and Therapeutic Options

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Author(s): Theodosis Kalamatianos, Despoina Denekou, George Stranjalis, Evangelia Papadimitriou*.

 

 

 

Abstract:

Background: Glioblastoma (GBM) is the most aggressive and common brain tumor in adults, currently lacking effective life-prolonging and recurrence-preventing therapy; median survival of GBM patients stands at only 14-16 months. Increasing lines of evidence indicate that Anaplastic lymphoma kinase (ALK), a druggable tyrosine kinase receptor over-expressed in GBM, represents a potential therapeutic target in this tumor.

Objective: An overview of the state of the art and the existing recent patents regarding potential exploitation of ALK as a therapeutic target and/or diagnostic/prognostic factor in GBM.

Method: Recent literature and patents focusing on or including ALK pre-clinical and clinical research in GBM have been identified and reviewed, and are discussed according to their potential use.

Results: Numerous recent ALK-related patents were identified. They were reviewed/analyzed in relation to previously published research and categorized based on their potential in GBM: i) diagnosis/ prognosis, ii) drug-based therapeutic targeting of ALK using a single compound or combination schemes and iii) therapeutic ALK targeting by other means, e.g. ALK vaccination.

Conclusion: ALK targeting holds promise as a novel therapeutic approach in GBM, especially in combination schemes allowing multi-target therapy. Such schemes may incorporate detection-guided therapy and utilize next generation inhibitory compounds with improved central nervous system penetration. Moreover, identification of ALK-mediated molecular pathway(s) related to GBM carcinogenesis/ pathology and putative therapy resistance is of high priority and warrants further exploitation.

 

READ MORE HERE: http://www.eurekaselect.com/159062

EDITOR’S CHOICE – Novel Patents Targeting Interleukin-17A; Implications in Cancer and Inflammation

Journal: Recent Patents on Anti-Cancer Drug Discovery

Author(s): Juan F. Santibanez*, Suncica Bjelica

Abstract:

Background: IL-17A is a founding member of the IL-17 family that has been implicated in the pathogenesis of inflammatory-associated diseases such as cancer and autoimmune disease. In cancer, IL-17A participates in many key events for tumor development, in part by affecting innate and adaptive immune system and also by direct modulation of many pro-tumor events. Moreover, IL-17A dysregulation at the site of inflammation is associated with rheumatoid arthritis, multiple sclerosis, psoriasis, among others. IL-17A has emerged as a topic of interest and is under profound investigation for its involvement in several types of inflammatory-associated diseases.

Objective: This review aims to present an overview of the state of the art of IL-17A role in cancer and inflammation, as well as to describe recent patents targeting IL-17A with relevant clinical and biological properties for the prevention and treatment of cancer and inflammatory diseases.

Methods: Relevant information was obtained by searching in PubMed using IL-17A or IL-17, cancer and inflammation as keywords, while relevant patents were obtained mainly from Google Patents.

Results: Literature data indicated IL-17A as important biomolecule in the physiopathology of cancer and inflammatory diseases. Whereas, novel patents (2010 to 2017) targeting IL-17A are focused mainly on describing strategies to modulate IL-17A per se, co-modulation by bispecific antibodies to blocking IL-17A and important cytokines for IL-17A functions, upstream mechanisms and compounds to regulate IL-17A expression.

Conclusion: The promising effects of patented agents against IL-17A may open new opportunities to therapeutic intervention targeting at different levels of involvement in the pathogenesis of cancer and inflammatory diseases.

Read more here: http://www.eurekaselect.com/159948/article

 

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