Purpose Of Review: Therapeutic alternatives to treat metastatic renal cell carcinoma (mRCC) are increasing, and combination therapies, including antiangiogenic agents and tyrosine kinase/mTOR/immune checkpoint inhibitors, are identified as the gold standard driven by the results of recent clinical studies. Nevertheless, the real-world RCC population is very heterogeneous, with categories of patients not represented in the enrolled trial population who may not benefit more from these treatments. The purpose of this expert review is to assess the rationale on which tyrosine kinase alone may still be a viable first-line treatment option for some subgroups of patients with mRCC.
Recent Findings: The first-line treatment with tyrosine kinase inhibitor monotherapy can still be considered an effective tool for addressing selected mRCCs, as highlighted by the successful outcome in a range of subjects such as favorable-risk patients, the ones suffering from autoimmune diseases, those with pancreatic or lung metastases, or previously undergoing organ transplantation and elderly subjects. Some selected categories of patients may still benefit from monotherapy with TKI, and smart sequential therapies can also be considered instead of a combination strategy. Tyrosine kinase inhibitors can also act as immune modulator agents, boosting the immune response to facilitate and potentiate the therapeutic effectiveness of subsequent immunotherapy.
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http://dx.doi.org/10.1007/s11912-021-01140-9 | DOI Listing |
ACS Appl Mater Interfaces
January 2025
Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, Guangdong 510060, P. R. China.
The clinical application of tyrosine kinase inhibitors (TKIs) is rapidly growing and has emerged as a cornerstone in the treatment of both solid tumors and hematologic malignancies. However, resistance to TKI targets and disease progression remain inevitable. Nanocarrier-mediated delivery has emerged as a promising strategy to overcome the limitations of the TKI application.
View Article and Find Full Text PDFSci Signal
January 2025
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
The small GTPase R-RAS2 regulates homeostatic proliferation and survival of T and B lymphocytes and, when present in high amounts, drives the development of B cell chronic lymphocytic leukemia. In normal and leukemic lymphocytes, R-RAS2 constitutively binds to antigen receptors through their immunoreceptor tyrosine-based activation motifs (ITAMs) and promotes tonic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Here, we examined the molecular mechanisms underlying this direct interaction and its consequences for R-RAS2 activity.
View Article and Find Full Text PDFPLoS Biol
January 2025
Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) CCT UNS-CONICET, Bahía Blanca, Argentina.
The DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, life span, and stress resistance. In Caenorhabditis elegans, DAF-2/IIS signaling is modulated by an extensive array of insulin-like peptides (ILPs) with diverse spatial and temporal expression patterns. However, the release dynamics and specific functions of these ILPs in adapting to different environmental conditions remain poorly understood.
View Article and Find Full Text PDFAsian Pac J Cancer Prev
January 2025
Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia.
Objective: Programmed cell death-1 (PD-1, encoded by PDCD1) regulatory network participates in glioblastoma multiforme development. However, such a network in trastuzumab-resistant human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains to be determined. Accordingly, this study was aimed to explore the PD-1 regulatory network responsible for the resistance of breast cancer cells to trastuzumab through a bioinformatics approach.
View Article and Find Full Text PDFAsian Pac J Cancer Prev
January 2025
S.P. Botkin City Clinical Hospital, Moscow, Russia.
Objectives: To study the predictive role of tumor-associated neutrophils in early luminal HER2-negative breast cancer.
Materials And Methods: This is a retrospective study conducted on 60 women cases aged from 31 to 79 years underwent surgery for luminal HER2-negative ductal breast cancer in tertiary care cancer centre. We first estimated basic morphological signs: tumor size, tumor grade (by Nottingham Histologic Score), tumor infiltrating lymphocytes (TILs), Lymphovascular invasion, hormonal receptors status, proliferative index, and regional lymph nodes metastasis.
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