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Serine/threonine-protein kinase B-Raf (BRAF) inhibitors are very effective in treating melanoma with BRAF mutations. BRAF inhibitors suppress aberrant growth of melanoma cells caused by BRAF mutations. BRAF mutations reportedly result in melanoma cells releasing immunosuppressive factors, and BRAF inhibitors elicit anti-melanoma immune responses by reducing such factors. However, immunological characteristics of tumor cells that acquire resistance to BRAF inhibitors remain unknown. Here, we compared immunological characteristics between a melanoma cell line and its vemurafenib-resistant subline. No differences were observed in the status of BRAF mutations, expression of surface molecules related to antitumor T-cell responses or recognition by human leukocyte antigen-A*0201-matched melanoma-specific cytotoxic T lymphocytes in a short-term co-culture assay. However, resistant tumor cells released high amounts of interleukin-10 depending on aberrant activation of Akt signaling, and dendritic cell functions were considerably suppressed by culture supernatants of the resistant cells. Our findings demonstrated a novel immunological mechanism contributing to tumor growth owing to drug resistance to BRAF inhibitors.
This article was published in the following journal.
Name: The Journal of dermatology
Anaplastic thyroid cancer (ATC), with 25% BRAFV600E mutation, is one of the most lethal human malignancies that currently has no effective therapy. Vemurafenib, a BRAFV600E inhibitor, has shown promis...
The BRAF inhibitor vemurafenib is widely used to treat melanomas harboring the activated BRAF mutation; however, vemurafenib showed poor efficacy in colon cancer, which impeded its clinical applicatio...
BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAFleads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a cur...
Acquired resistance against doxorubicin is a major limitation in clinical treatment of breast cancer. The molecular mechanism behind the aberrant expression of genes leading to doxorubicin resistance ...
RATIONALE: Measuring levels of interleukin-6 and depression may help doctors understand the relationship between interleukin-6 and depression. It may also help the study of cancer in the f...
Vemurafenib is an anti-cancer treatment indicated as monotherapy in the treatment of adult patients with non-resectable or metastatic melanoma carrying a BRAF V600 mutation. Cobimetinib i...
The goal of this clinical research study is to learn about how vemurafenib may affect certain biomarkers in patients with PTC. Biomarkers are in the blood/tissue and may be related to you...
This study evaluates whether it is safe to administer a peptide vaccine with vemurafenib. This study will also evaluate the effects of the combination of the peptide vaccine and vemurafeni...
The goal of this clinical research study is to find the highest tolerable dose of vemurafenib that can be given in combination with cetuximab and irinotecan to patients with advanced cance...
Receptors present on a wide variety of hematopoietic and non-hematopoietic cell types that are specific for INTERLEUKIN-4. They are involved in signaling a variety of immunological responses related to allergic INFLAMMATION including the differentiation of TH2 CELLS and the regulation of IMMUNOGLOBULIN E production. Two subtypes of receptors exist and are referred to as the TYPE I INTERLEUKIN-4 RECEPTOR and the TYPE II INTERLEUKIN-4 RECEPTOR. Each receptor subtype is defined by its unique subunit composition.
An interleukin receptor subunit that was originally discovered as a component of the INTERLEUKIN 2 RECEPTOR. It was subsequently found to be a component of several other receptors including the INTERLEUKIN 4 RECEPTOR, the INTERLEUKIN 7 RECEPTOR, the INTERLEUKIN-9 RECEPTOR, the INTERLEUKIN-15 RECEPTOR, and the INTERLEUKIN-21 RECEPTOR. Mutations in the gene for the interleukin common gamma chain have been associated with X-LINKED COMBINED IMMUNODEFICIENCY DISEASES.
A lymphohematopoietic cytokine that plays a role in regulating the proliferation of ERYTHROID PRECURSOR CELLS. It induces maturation of MEGAKARYOCYTES which results in increased production of BLOOD PLATELETS. Interleukin-11 was also initially described as an inhibitor of ADIPOGENESIS of cultured preadipocytes.
Cell surface receptors for INTERLEUKIN-13. Included under this heading are the INTERLEUKIN-13 RECEPTOR ALPHA2 which is a monomeric receptor and the INTERLEUKIN-4 RECEPTOR TYPE II which has specificity for both INTERLEUKIN-4 and INTERLEUKIN-13.
A cytokine subunit that is a component of both interleukin-12 and interleukin-23. It binds to the INTERLEUKIN-12 SUBUNIT P35 via a disulfide bond to form interleukin-12 and to INTERLEUKIN-23 SUBUNIT P19 to form interleukin-23.
Mergers & Acquisitions
Commercial and market reports on mergers and acquisitions in the biotechnology, pharmaceutical, medical device and life-science industries. Mergers and acquisitions (abbreviated M&A;) is an aspect of corporate strategy, corporate finance and manageme...
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