Abstract:
:Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells. Ibrutinib (PCI-32765) is an orally available small molecule that acts as an inhibitor of the BTK and is approved for the treatment of patients with some hematological malignancies. It has been suggested that ibrutinib may also have a potential antitumor activity in solid neoplasms. In this sense, ibrutinib has the ability to revert polarization of TCD4+ to Th1 lymphocytes to increase the cytotoxic ability of T CD8+ and to regulate tumor-induced immune tolerance by acting over tumor infiltrating cells activity and immunosuppressive cytokines release. Furthermore, based on its molecular activity and safety, ibrutinib has been considered as a partner for treatment combination with PI3K/AKT/mTOR inhibitors or with immune-checkpoint inhibitors, inhibiting immunosuppressive signals from the tumor microenvironment, and overcoming the immune resistance to current anti-PD1/PDL1 immunotherapeutic drugs by the CXCR4/CXCL2 pathway regulation. Currently, a broad range of different studies are evaluating the activity of ibrutinib either as single agent or in combination in patients with solid tumors.
journal_name
Cancer Treat Revjournal_title
Cancer treatment reviewsauthors
Molina-Cerrillo J,Alonso-Gordoa T,Gajate P,Grande Edoi
10.1016/j.ctrv.2017.06.001subject
Has Abstractpub_date
2017-07-01 00:00:00pages
41-50eissn
0305-7372issn
1532-1967pii
S0305-7372(17)30099-3journal_volume
58pub_type
杂志文章,评审abstract::Chest wall breast cancer recurrence after mastectomy is a disease difficult to treat. Its incidence varies between 5% and 30% in different subset of patients. When possible, radical surgical therapy represents the main treatment approach, however when the disease progresses and/or treatments are not successful, ulcera...
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pub_type: 历史文章,杂志文章,评审
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pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章,评审
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更新日期:2014-03-01 00:00:00