scholarly journals Kinase Inhibitors: Adverse Effects Related to the Endocrine System

2013 ◽  
Vol 98 (4) ◽  
pp. 1333-1342 ◽  
Author(s):  
Maya B. Lodish
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Signaling Pathways ◽  
Anticancer Agents ◽  
Fetal Development ◽  
Linear Growth ◽  
Kinase Inhibitors ◽  
Evidence Synthesis ◽  
Endocrine System ◽  
Cancer Therapeutics

Context: The use of kinase inhibitors (KIs) in the treatment of cancer has become increasingly common, and practitioners must be familiar with endocrine-related side effects associated with these agents. This review provides an update to the clinician regarding the management of potential endocrinological effects of KIs. Evidence Acquisition: PubMed was employed to identify relevant manuscripts. A review of the literature was conducted, and data were summarized and incorporated. Evidence Synthesis: KIs, including small molecule KIs and monoclonal antibodies directed against kinases, have emerged over the past decade as an important class of anticancer agents. KIs specifically interfere with signaling pathways that are dysregulated in certain types of cancers and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. Currently, at least 20 KIs are approved as cancer therapeutics. However, KIs may affect a broad spectrum of targets and may have additional, unidentified mechanisms of action at the cellular level due to overlap between signaling pathways in the tumor cell and endocrine system. Recent reports in the literature have identified side effects associated with KIs, including alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, adrenal function, and glucose metabolism. Conclusions: Clinicians need to monitor the thyroid functions of patients on KIs. In addition, bone density and vitamin D status should be assessed. Special care should be taken to follow linear growth and development in children taking these agents. Clinicians should counsel patients appropriately on the potential adverse effects of KIs on fetal development.

scholarly journals Endocrine side effects of broad-acting kinase inhibitors

2010 ◽  
Vol 17 (3) ◽  
pp. R233-R244 ◽  
Author(s):  
Maya B Lodish ◽  
Constantine A Stratakis
Keyword(s):  
Targeted Therapy ◽  
Side Effects ◽  
Glucose Metabolism ◽  
Cancer Therapy ◽  
Fetal Development ◽  
Linear Growth ◽  
Kinase Inhibitors ◽  
Mechanisms Of Action ◽  
Cellular Level ◽  
Gonadal Function

Targeted therapy in oncology consists of drugs that specifically interfere with abnormal signaling pathways that are dysregulated in cancer cells. Tyrosine kinase inhibitors (TKIs) take advantage of unique oncogenes that are activated in certain types of cancer, and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. However, many kinase inhibitors for cancer therapy are somewhat nonselective, and most have additional mechanisms of action at the cellular level, which are not completely understood. The use of these agents has increased our knowledge of important side effects, of which the practicing clinician must be aware. Recently, proposed endocrine-related side effects of these agents include alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, and glucose metabolism, and adrenal function. This review summarizes the most recent data on the endocrine side effects of TKIs.

Safe and Effective Kinase Inhibitors for the Treatment of Gynecological Cancers: In Silico Approach

2021 ◽  
Vol 22 ◽  
Author(s):  
Vaishali M. Patil ◽  
Abhishek Kumar ◽  
Vaishali Anand ◽  
Priya Bansal ◽  
Neeraj Masand
Keyword(s):  
Mortality Rate ◽  
Anticancer Agents ◽  
In Silico ◽  
Kinase Inhibitors ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Cancer Therapeutics ◽  
Cancer Drugs ◽  
Gynecological Cancers ◽  
Anti Cancer

Aims: To study various types of gynecological cancers and the available therapeutics to investigate safe and effective drugs. Background: Cancer is the most common cause of mortality throughout the world. When the statistics is considered for gynecological cancers, ovarian, cervical and uterine cancers are among the most prevalent types. They have worst prognosis and the highest mortality rate and by the year 2040 significant increase in mortality rate is predicted. Objective: The major limitation with development of anti-cancer therapeutics for the gynecological cancers are safety of the therapeutics for the developing fetus as well as the mother. Various medicinal classes of natural to synthetic therapeutics have been reported including kinase inhibitors as the most promising category of anti-cancer drugs. Method: A dataset of kinase inhibitory clinically approved anticancer agents was derived through literature review. A QSAR based approach i.e. VEGAQSAR has been applied to evaluate the reproductive and developmental toxicity for the selected class of kinase inhibitors. Result: In the present work, the promising category of anticancer kinase inhibitors has been investigated for its toxicity potential with the help of in silico approach. The anti-cancer kinase inhibitors were categorized based on the found non-toxic or toxic properties towards reproductive and developmental toxicity. Conclusion: Early prediction of the available or proposed anti-cancer therapeutics for their contribution towards developmental and reproductive toxicity is an important criterion for their use in pregnancy associated cancers. The investigation of toxicity profile of available anti-cancer kinase therapeutics will be helpful to design and develop novel and safe anti-cancer drugs in the near future. Other: The study outcomes will benefit the current anticancer drug development efforts.

Green Approaches for Cancer Management: an Effective Tool for Health Care

2021 ◽  
Vol 21 ◽  
Author(s):  
Jitendra Gupta ◽  
Ashima Ahuja ◽  
Reena Gupta
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Cell Apoptosis ◽  
Cancer Therapeutics ◽  
Modern Society ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Structure Generation ◽  
Cancer Management ◽  
Green Approach

Background: Cancer is one of the leading causes of an increasing number of death incidences in modern society. As the population increases, there is increased thrust for screening newer anticancer (phytoconstituents) agents to manage cancers. Around 35000 herbal phytoconstituents are obtained from plants, animals and marine sources to create awareness of green therapy in managing, reducing, minimizing side effects of modern chemotherapeutics and radiation therapy. The herbal plants are the richest sources of natural remedies and bioactive compounds that promote medicines' alternative systems as a green approach for managing various cancers. The terpenoids, saponins, volatile oils, and flavonoid phytoconstituents are most efficiently used to manage cancer with minimal side effects. Objective: The objectives of the present study are to investigate the efficacious, potent and safe use of herbal phytoconstituents extracts in the management of cancers and study their mechanism of action through alteration of transcription proteins, blocking G-2/M phase, distortion of tubulin structure, generation of reactive oxygen species, lipid peroxidation, cell cycle arrest, anti-proliferation induced cell apoptosis for target specific cancer treatment. The information was collected from databases such as ScienceDirect, PubMed, Google Scholar, Academia, MedLine, and WoS. Methods: The Literature was surveyed and screened keywords like cancer therapeutics, metastasis, proliferation, cell apoptosis, cell lines, phytoconstituents for cancer management, and related disorders. Results: The findings suggested that the crude extracts act as an antioxidant, free radical scavenger, or anti-aging agent exploited in the management of cancers along with treatment of other infectious diseases like ulcers, gout, liver diseases, respiratory tract infection, renal disorders, blood disorders, CVD, anti-inflammatory and several wound infections. Conclusion: The phytoactive moieties having herbal extracts help improve the compromised immunity status of affected patients and provide measures for scientific studies of newer anticancer agents in herbal industries.

Identification of target small molecule tyrosine kinase inhibitors that need monitoring and clinical application of protocol for early detection of cancer therapeutics-related cardiac dysfunction using signal detection: An investigation of real world data

2020 ◽  
pp. 107815522093036
Author(s):  
Takahito Mizuno ◽  
Takamasa Sakai ◽  
Kouichi Tanabe ◽  
Koji Kozaki ◽  
Takumi Umemura ◽  
...  
Keyword(s):  
Side Effects ◽  
Early Detection ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Signal Detection ◽  
Tyrosine Kinase Inhibitors ◽  
Cardiac Dysfunction ◽  
Kinase Inhibitors ◽  
Package Insert ◽  
Cancer Therapeutics

Purpose In order to detect cancer therapeutics-related cardiac dysfunction (CTRCD) early, we identified which drugs were to be monitored using signal detection and the package insert, and created and applied a protocol to address this. Methods Adverse event data recorded in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and January 2018 were used. Among small molecule tyrosine kinase inhibitors that are not described in the serious side-effects section of the package insert despite signal detection, tyrosine kinase inhibitors with severe side-effects in the background of cases reported by JADER database were selected to be monitored in clinical practice. We applied our findings clinically by creating a protocol to detect CTRCD early. All cases at Tosei General Hospital where the target tyrosine kinase inhibitors were administered from when they were first released in November 2019 were included. We compared the results from before and after we began the protocol to clarify its effects. Results We found that CTRCD was not described in the serious side-effect section of the package inserts for Bosutinib, Alectinib, and Osimertinib even though CTRCD signals were detected for them. Therefore, it is possible that we may have previously overlooked CTRCD. When we applied our protocol using Osimertinib as the target drug, we were able to detect CTRCD early in 5/21 (24%) patients. Conclusions It was clarified that the drug identification method used in this study for early detection of adverse events leads to early detection of adverse events when applied clinically.

Nitrogen-Containing Heterocycles as Anticancer Agents: An Overview

2020 ◽  
Vol 20 (18) ◽  
pp. 2150-2168 ◽  
Author(s):  
Damanpreet K. Lang ◽  
Rajwinder Kaur ◽  
Rashmi Arora ◽  
Balraj Saini ◽  
Sandeep Arora
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Building Blocks ◽  
Basic Structure ◽  
Present Review ◽  
Cancer Drugs ◽  
Biological Compounds ◽  
Anti Cancer ◽  
Structural Search

Background: Cancer is spreading all over the world, and it is becoming the leading cause of major deaths. Today’s most difficult task for every researcher is to invent a new drug that can treat cancer with minimal side effects. Many factors, including pollution, modern lifestyle and food habits, exposure to oncogenic agents or radiations, enhanced industrialization, etc. can cause cancer. Treatment of cancer is done by various methods that include chemotherapy, radiotherapy, surgery and immunotherapy in combination or singly along with kinase inhibitors. Most of the anti-cancer drugs use the concept of kinase inhibition. Objective: The number of drugs being used in chemotherapy has heterocycles as their basic structure in spite of various side effects. Medicinal chemists are focusing on nitrogen-containing heterocyclic compounds like pyrrole, pyrrolidine, pyridine, imidazole, pyrimidines, pyrazole, indole, quinoline, oxadiazole, azole, benzimidazole, etc. as the key building blocks to develop active biological compounds. The aim of this study is to attempt to compile a dataset of nitrogen-containing heterocyclic anti-cancer drugs. Methods: We adopted a structural search on notorious journal publication websites and electronic databases such as Bentham Science, Science Direct, PubMed, Scopus, USFDA, etc. for the collection of peer-reviewed research and review articles for the present review. The quality papers were retrieved, studied, categorized into different sections, analyzed and used for article writing. Conclusion: As per FDA databases, nitrogen-based heterocycles in the drug design are almost 60% of unique small-molecule drugs. Some of the nitrogen-containing heterocyclic anti-cancer drugs are Axitinib, Bosutinib, Cediranib, Dasatanib (Sprycel®), Erlotinib (Tarceva®), Gefitinib (Iressa®), Imatinib (Gleevec®), Lapatinib (Tykerb ®), Linifanib, Sorafenib (Nexavar®), Sunitinib (Sutent®), Tivozanib, etc. In the present review, we shall focus on the overview of nitrogen-containing heterocyclic active compounds as anti-cancer agents.

scholarly journals Safety and Efficacy Profile of Asciminib As Treatment in Chronic Myeloid Leukemia Patients after Several Tyrosine-Kinase Inhibitors Failure

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 49-50
Author(s):  
Alejandro Luna ◽  
Natalia Estrada ◽  
Concepcion Boque ◽  
Blanca Xicoy ◽  
Pilar Giraldo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Adverse Effects ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Compassionate Use ◽  
Safety And Efficacy ◽  
Efficacy Profile

Introduction: Asciminib is a new BCR-ABL1 inhibitor that differs from previous tyrosine kinase inhibitors (TKIs) in that it does not bind to the ATP-binding site of the kinase. Data from different clinical trials has shown an adequate safety and efficacy profile in chronic myeloid leukemia (CML) patients failing previous TKIs. However, no findings have been communicated in real life experience. The aim of our study is to present first results of asciminib in CML patients failing previous TKIs under the current compassionate use program. Methods: We retrospectively collected data from 31 patients treated with asciminib in 25 centers under compassionate use program. Data collecting was performed between October 2018 and June 2020. Patients baseline characteristics are shown in table 1. Most patients were heavily pretreated with 28 patients receiving 3 or more TKIs previous to asciminib. Eleven patients (35.5%) had been treated with ponatinib at some point throughout the disease. Twelve patients showed BCR-ABL1 mutations (only 1 case with T315I mutation). Switch to asciminib was due to intolerance in 22 patients and due to resistance in the remaining 9. Median dose of asciminib was 80mg per day (40mg every 12 hours). Treatment responses were evaluated according to European Leukemia Net recommendations. Data compilation and analysis were performed with REDCap Software and IBM SPSS (Version 25.0). Results: Median time on asciminib for the entire cohort was 35 weeks. Regarding toxicities, 13 patients (42%) experienced mild extra-hematological side effects (grade 1-2) being the most frequent fatigue (19%), joint pain (16%) and nausea (9%). Four patients (12,9%) showed severe (grade 3-4) extra-hematological events: fatigue, hepatotoxicity, hypertension and pericardial effusion (1 patient each). Three patients (9,7%) suffered from grade 4 thrombocytopenia, 2 of them associating grade 4 neutropenia. All toxicities according to previous TKIs adverse effects as well as cross-intolerance data is shown in table 2. Dose reduction had to be carried out in 9 patients (29%), 7 of those with temporary treatment interruptions; most owing to hematological adverse effects. In terms of efficacy (Graph 1), probability of reaching or at least maintaining previous response was 100%, 61.3% and 35.5% for complete hematological response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR), respectively. Regarding probabilities to improve previous responses, rates of CCyR and MMR were, respectively, 22,2% (2/9) and 22,2% (2/9) for resistant patients and 44% (4/9) and 62,5%. (10/16) for intolerant group. Amid the 11 patients previously treated with ponatinib, 3 patients (27,3%) showed improvement of response achieving at least MMR, 2 of them from the TKI-intolerant group and 1 from the TKI-resistant group. The median follow-up time was 40 weeks, after which 27 patients (87.1%) continued with asciminib. Treatment cessation happened in 2 patients due to progression to blastic phase and in 2 patients due to lack of efficacy. No patients discontinued due to side effects. Conclusion: The data presented, similar to that known from clinical trials, supports the use of asciminib in routine clinical practice in CML patients failing to previous TKIs. Disclosures Garcia-Gutiérrez: Novartis: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Incyte: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding.

Side effects of tyrosine kinase inhibitors (TKIs) on bone remodelling

2012 ◽  
Vol 224 (03) ◽  
Author(s):  
JT Tauer ◽  
A Ulmer ◽  
LC Hofbauer ◽  
M Suttorp
Keyword(s):  
Side Effects ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Bone Remodelling

Src Kinase Inhibitors: Promising Cancer Therapeutics?

2012 ◽  
Vol 17 (2) ◽  
pp. 145-159 ◽  
Author(s):  
Helen Creedon ◽  
Valerie G . Brunton
Keyword(s):  
Kinase Inhibitors ◽  
Src Kinase ◽  
Cancer Therapeutics

A Brief Review on the Development of Novel Potentially Active Azetidin-2-ones Against Cancer

2020 ◽  
Vol 24 (5) ◽  
pp. 473-486 ◽  
Author(s):  
Ligia S. da Silveira Pinto ◽  
Thatyana R. Alves Vasconcelos ◽  
Claudia Regina B. Gomes ◽  
Marcus Vinícius N. de Souza
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Present Review ◽  
Pharmacological Properties ◽  
Important Group ◽  
Wide Range ◽  
Anti Inflammatory

Azetidin-2-ones (β-lactams) and its derivatives are an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, anticancer, anti-diabetic, anti-inflammatory and anticonvulsant. Efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. The present review aimed to highlight some recent discoveries (2013-2019) on the development of novel azetidin-2-one-based compounds as potential anticancer agents.

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