Diarrhea Induced by Small Molecule Tyrosine Kinase Inhibitors Compared With Chemotherapy: Potential Role of the Microbiome

Small molecule receptor tyrosine kinase inhibitors (SM-TKIs) are among a group of targeted cancer therapies, intended to be more specific to cancer cells compared with treatments, such as chemotherapy, hence reducing adverse events. Unfortunately, many patients report high levels of diarrhea, the pathogenesis of which remains under investigation. In this article, we compare the current state of knowledge of the pathogenesis of chemotherapy-induced diarrhea (CID) in comparison to SM-TKI–induced diarrhea, and investigate how a similar research approach in both areas may be beneficial. To this end, we review evidence that both treatment modalities may interact with the gut microbiome, and as such the microbiome should be investigated for its ability to reduce the risk of diarrhea.

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The role of small molecule Kit protein-tyrosine kinase inhibitors in the treatment of neoplastic disorders

Pharmacological Research ◽

10.1016/j.phrs.2018.04.020 ◽

2018 ◽

Vol 133 ◽

pp. 35-52 ◽

Cited By ~ 28

Author(s):

Robert Roskoski

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Small Molecule ◽

Protein Tyrosine Kinase ◽

Kinase Inhibitors ◽

Protein Tyrosine ◽

Neoplastic Disorders

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The role of ethnicity in personalized dosing of small molecule tyrosine kinase inhibitors used in oncology

Translational Cancer Research ◽

10.21037/tcr.2017.09.09 ◽

2017 ◽

Vol 6 (S10) ◽

pp. S1558-S1591 ◽

Cited By ~ 4

Author(s):

Josephine A. Touma ◽

Andrew J. McLachlan ◽

Annette S. Gross

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Small Molecule ◽

Kinase Inhibitors

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The role of small molecule Flt3 receptor protein-tyrosine kinase inhibitors in the treatment of Flt3-positive acute myelogenous leukemias

Pharmacological Research ◽

10.1016/j.phrs.2020.104725 ◽

2020 ◽

Vol 155 ◽

pp. 104725 ◽

Cited By ~ 3

Author(s):

Robert Roskoski

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Small Molecule ◽

Protein Tyrosine Kinase ◽

Kinase Inhibitors ◽

Receptor Protein ◽

Protein Tyrosine ◽

Acute Myelogenous ◽

Receptor Protein Tyrosine Kinase

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Vascular Impact of Cancer Therapies: The Case of BTK (Bruton Tyrosine Kinase) Inhibitors

Circulation Research ◽

10.1161/circresaha.121.318259 ◽

2021 ◽

Vol 128 (12) ◽

pp. 1973-1987

Author(s):

Matthew R. Fleming ◽

Ling Xiao ◽

Klarissa D. Jackson ◽

Joshua A. Beckman ◽

Ana Barac ◽

...

Keyword(s):

Atrial Fibrillation ◽

Side Effects ◽

Tyrosine Kinase ◽

Small Molecule ◽

Kinase Inhibitors ◽

Cardiovascular Complications ◽

Cancer Therapies ◽

Bruton Tyrosine Kinase ◽

Targeted Cancer Therapies ◽

Btk Inhibitors

Novel targeted cancer therapies have revolutionized oncology therapies, but these treatments can have cardiovascular complications, which include heterogeneous cardiac, metabolic, and vascular sequelae. Vascular side effects have emerged as important considerations in both cancer patients undergoing active treatment and cancer survivors. Here, we provide an overview of vascular effects of cancer therapies, focusing on small-molecule kinase inhibitors and specifically inhibitors of BTK (Bruton tyrosine kinase), which have revolutionized treatment and prognosis for B-cell malignancies. Cardiovascular side effects of BTK inhibitors include atrial fibrillation, increased risk of bleeding, and hypertension, with the former 2 especially providing a treatment challenge for the clinician. Cardiovascular complications of small-molecule kinase inhibitors can occur through either on-target (targeting intended target kinase) or off-target kinase inhibition. We will review these concepts and focus on the case of BTK inhibitors, highlight the emerging data suggesting an off-target effect that may provide insights into development of arrhythmias, specifically atrial fibrillation. We believe that cardiac and vascular sequelae of novel targeted cancer therapies can provide insights into human cardiovascular biology.

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Tyrosine Kinase Inhibitors;an approach for targeted cancer therapies-A Review

International Journal of Livestock Research ◽

10.5455/ijlr.20200608021211 ◽

2020 ◽

pp. 1

Author(s):

Arpita Shrivastav ◽

Neeraj Shrivastava

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Cancer Therapies ◽

Targeted Cancer Therapies

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Reactive Oxygen Species-Mediated Mechanisms of Action of Targeted Cancer Therapy

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/1485283 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 50

Author(s):

Hanna-Riikka Teppo ◽

Ylermi Soini ◽

Peeter Karihtala

Keyword(s):

Reactive Oxygen Species ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Reactive Oxygen ◽

Current Evidence ◽

Cancer Therapies ◽

Oxygen Species ◽

Mediated Effects ◽

Targeted Cancer Therapies

Targeted cancer therapies, involving tyrosine kinase inhibitors and monoclonal antibodies, for example, have recently led to substantial prolongation of survival in many metastatic cancers. Compared with traditional chemotherapy and radiotherapy, where reactive oxygen species (ROS) have been directly linked to the mediation of cytotoxic effects and adverse events, the field of oxidative stress regulation is still emerging in targeted cancer therapies. Here, we provide a comprehensive review regarding the current evidence of ROS-mediated effects of antibodies and tyrosine kinase inhibitors, use of which has been indicated in the treatment of solid malignancies and lymphomas. It can be concluded that there is rapidly emerging evidence of ROS-mediated effects of some of these compounds, which is also relevant in the context of drug resistance and how to overcome it.

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A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

Era s journal of medical research ◽

10.24041/ejmr2020.34 ◽

2020 ◽

Vol 7 (2) ◽

pp. 205-211

Author(s):

Kaynat Fatima ◽

Syed Tasleem Raza ◽

Ale Eba ◽

Sanchita Srivastava ◽

Farzana Mahdi

Keyword(s):

Chronic Myeloid Leukemia ◽

Tyrosine Kinase ◽

Protein Kinases ◽

Tyrosine Kinase Inhibitors ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Line Treatment ◽

First Line ◽

First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

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