FDA approves CSF1R inhibitor for rare, non-cancerous joint tumours
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Associations of mucinous differentiation and mucin expression with immune cell infiltration and prognosis in colorectal adenocarcinoma
The production of extracellular mucus and expression of mucins are commonly aberrant in colorectal cancer, yet their roles in tumour progression remain unclear.
Systemic HER3 ligand-mimicking nanobioparticles enter the brain and reduce intracranial tumour growth
Crossing the blood–brain barrier (BBB) and reaching intracranial tumours is a clinical challenge for current targeted interventions including antibody-based therapies, contributing to poor patient outcomes. Increased cell surface density of human epidermal growth factor receptor 3 (HER3) is associated with a growing number of metastatic tumour types and is observed on tumour cells that acquire resistance to a growing number of clinical targeted therapies. Here we describe the evaluation of HER3-homing nanobiological particles (nanobioparticles (NBPs)) on such tumours in preclinical models and our discovery that systemic NBPs could be found in the brain even in the absence of such tumours. Our subsequent studies described here show that HER3 is prominently associated with both mouse and human brain endothelium and with extravasation of systemic NBPs in mice and in human-derived BBB chips in contrast to non-targeted agents. In mice, systemically delivered NBPs carrying tumoricidal agents reduced the growth of intracranial triple-negative breast cancer cells, which also express HER3, with improved therapeutic profile compared to current therapies and compared to agents using traditional BBB transport routes. As HER3 associates with a growing number of metastatic tumours, the NBPs described here may offer targeted efficacy especially when such tumours localize to the brain.
Loss of ARID1A accelerates prostate tumourigenesis with a proliferative collagen-poor phenotype through co-operation with AP1 subunit cFos
Prostate cancer (PC) is the commonest male visceral cancer, and second leading cause of cancer mortality in men in the Western world.
A detoxified TLR4 agonist inhibits tumour growth and lung metastasis of osteosarcoma by promoting CD8+ cytotoxic lymphocyte infiltration
Osteosarcoma is the most common malignant bone tumour with limited treatment options and poor outcomes in advanced metastatic cases. Current immunotherapies show limited efficacy, highlighting the need for novel therapeutic approaches. Systemic immune activation by Toll-like receptor 4 (TLR4) immunostimulants has shown great promise; however, current TLR4 agonists’ toxicity hinders this systemic approach in patients with osteosarcoma.
Targeting of TAMs: can we be more clever than cancer cells?
With increasing incidence and geography, cancer is one of the leading causes of death, reduced quality of life and disability worldwide. Principal progress in the development of new anticancer therapies, in improving the efficiency of immunotherapeutic tools, and in the personification of conventional therapies needs to consider cancer-specific and patient-specific programming of innate immunity. Intratumoral TAMs and their precursors, resident macrophages and monocytes, are principal regulators of tumor progression and therapy resistance. Our review summarizes the accumulated evidence for the subpopulations of TAMs and their increasing number of biomarkers, indicating their predictive value for the clinical parameters of carcinogenesis and therapy resistance, with a focus on solid cancers of non-infectious etiology. We present the state-of-the-art knowledge about the tumor-supporting functions of TAMs at all stages of tumor progression and highlight biomarkers, recently identified by single-cell and spatial analytical methods, that discriminate between tumor-promoting and tumor-inhibiting TAMs, where both subtypes express a combination of prototype M1 and M2 genes. Our review focuses on novel mechanisms involved in the crosstalk among epigenetic, signaling, transcriptional and metabolic pathways in TAMs. Particular attention has been given to the recently identified link between cancer cell metabolism and the epigenetic programming of TAMs by histone lactylation, which can be responsible for the unlimited protumoral programming of TAMs. Finally, we explain how TAMs interfere with currently used anticancer therapeutics and summarize the most advanced data from clinical trials, which we divide into four categories: inhibition of TAM survival and differentiation, inhibition of monocyte/TAM recruitment into tumors, functional reprogramming of TAMs, and genetic enhancement of macrophages.
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