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The abnormal tumor vasculature is one of key reasons that lead to the limited tumor perfusion as well as hypoxic and immunosuppressive tumor microenvironment (TME). Herein, we uncover that by normalizing the tumor vasculature with erlotinib, a specific inhibitor of epidermal growth factor receptor (EGFR), the tumor perfusion and tumor oxygenation statuses in different types of tumors including murine breast tumors, colorectal tumors, and squamous cell carcinoma tumors, could be remarkably enhanced. As the results, the tumor uptake of drug-loaded nanoparticles as well as their interstitial penetration within the tumor would be greatly increased for mice pre-treated with erlotinib at the oral feeding dose of 50 mg/kg, leading to remarkably improved chemotherapeutic efficacy of nanomedicine. On the other hand, owing to the erlotinib-induced normalization of tumor vasculatures, the relieved hypoxic state in the three different types of tumors could alter the immunosuppressive TME into immunosupportive. Such an effect together with the increased tumor retention of anti-PDL1 antibody, a clinically approved checkpoint blockade agent, finally contributes to the greatly improved tumor inhibition effect in cancer immunotherapy. Therefore, our work presents a general yet effective strategy using a clinical drug to enhance the efficacies of cancer nanomedicine and immunotherapy by normalizing tumor vasculatures and modulating TME.
This article was published in the following journal.
A defining hallmark of cancer and cancer development is upregulated angiogenesis. The vasculature formed in tumors is structurally abnormal, not organized in the conventional hierarchical arrangement,...
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RATIONALE: Biological therapies such as erlotinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Monoclonal antibodies such as trastuzumab can locate tu...
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blockin...
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: This phase II trial is studying how well erlotinib works in treat...
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help ...
The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth.
Hypoxic conditions in tumor cells due to the tumor outgrowing its blood supply. It is associated with increased METASTASIS and resistance to RADIOTHERAPY and DRUG THERAPY.
An unusual and aggressive tumor of germ-cell origin that reproduces the extraembryonic structures of the early embryo. It is the most common malignant germ cell tumor found in children. It is characterized by a labyrinthine glandular pattern of flat epithelial cells and rounded papillary processes with a central capillary (Schiller-Duval body). The tumor is rarely bilateral. Before the use of combination chemotherapy, the tumor was almost invariably fatal. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1189)
Subpopulation of heterogeneous fibroblasts within the TUMOR MICROENVIRONMENT that support NEOPLASTIC CELL TRANSFORMATION and NEOPLASTIC PROCESSES.
A tumor, basically a carcinoma with a single sarcoma such as leiomyosarcoma or angiosarcoma or multiple sarcomas of uterine origin. The role of estrogen has been postulated as a possible etiological factor in this tumor. (Holland et al., Cancer Medicine, 3d ed, p1703)
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Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...
Track and monitor developments in breast cancer research and commercial development. Follow the tabs above to read the latest global news, research, clinical trials on breast cancer and follow companies active in the development of breast cancer tr...