scholarly journals Pulmonary sarcomatoid carcinoma: progress, treatment and expectations

2020 ◽  
Vol 12 ◽  
pp. 175883592095020
Author(s):  
Xin Li ◽  
Di Wu ◽  
Hongyu Liu ◽  
Jun Chen
Keyword(s):  
Cell Death ◽  
Growth Factor ◽  
Programmed Cell Death ◽  
Treatment Options ◽  
Sarcomatoid Carcinoma ◽  
Growth Factor Receptor ◽  
Anaplastic Lymphoma ◽  
Epidermal Growth ◽  
Pulmonary Sarcomatoid Carcinoma ◽  
Endothelial Growth Factor

Pulmonary sarcomatoid carcinoma (PSC) is a unique, highly invasive pulmonary malignancy with a poor prognosis, representing 0.1–0.4% of all malignant lung tumors. Because of its highly aggressive character and propensity for frequent metastasis, PSC shows low response rates to traditional treatments such as chemotherapy, radiotherapy, and neoadjuvant therapy. In recent years, considerable progress has been made in gene sequencing, targeted therapies, and immunotherapies. One of the most promising treatment approaches is the selection of mono-targeted or multi-targeted drugs according to tumor gene-mutation sites, such as epidermal growth factor receptor or vascular endothelial growth factor receptor 2 ( EGFR/VEGFR2), anaplastic lymphoma kinase ( ALK), and others. Another approach is the activation of therapeutic anti-tumor immunity via pathways including programmed cell-death protein-1/programmed cell-death ligand-1 ( PD-1/PD-L1), which has been used in individual cases. In this review, we will introduce the clinicopathologic features, molecular typing, and traditional treatments. We will also review the biological characteristics and the latest therapies for PSC. These novel therapies show promise in the management of PSC, and the outcomes of investigative trials will hopefully reveal a variety of treatment options for patients with PSC.

scholarly journals Combined antiangiogenic and anti–PD-L1 therapy stimulates tumor immunity through HEV formation

2017 ◽  
Vol 9 (385) ◽  
pp. eaak9679 ◽  
Author(s):  
Elizabeth Allen ◽  
Arnaud Jabouille ◽  
Lee B. Rivera ◽  
Inge Lodewijckx ◽  
Rindert Missiaen ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Death ◽  
Growth Factor ◽  
Programmed Cell Death ◽  
Antiangiogenic Therapy ◽  
Growth Factor Receptor ◽  
Cytotoxic T Cell ◽  
Vascular Endothelial ◽  
High Endothelial Venules ◽  
Endothelial Growth Factor

Inhibitors of VEGF (vascular endothelial growth factor)/VEGFR2 (vascular endothelial growth factor receptor 2) are commonly used in the clinic, but their beneficial effects are only observed in a subset of patients and limited by induction of diverse relapse mechanisms. We describe the up-regulation of an adaptive immunosuppressive pathway during antiangiogenic therapy, by which PD-L1 (programmed cell death ligand 1), the ligand of the negative immune checkpoint regulator PD-1 (programmed cell death protein 1), is enhanced by interferon-γ–expressing T cells in distinct intratumoral cell types in refractory pancreatic, breast, and brain tumor mouse models. Successful treatment with a combination of anti-VEGFR2 and anti–PD-L1 antibodies induced high endothelial venules (HEVs) in PyMT (polyoma middle T oncoprotein) breast cancer and RT2-PNET (Rip1-Tag2 pancreatic neuroendocrine tumors), but not in glioblastoma (GBM). These HEVs promoted lymphocyte infiltration and activity through activation of lymphotoxin β receptor (LTβR) signaling. Further activation of LTβR signaling in tumor vessels using an agonistic antibody enhanced HEV formation, immunity, and subsequent apoptosis and necrosis in pancreatic and mammary tumors. Finally, LTβR agonists induced HEVs in recalcitrant GBM, enhanced cytotoxic T cell (CTL) activity, and thereby sensitized tumors to antiangiogenic/anti–PD-L1 therapy. Together, our preclinical studies provide evidence that anti–PD-L1 therapy can sensitize tumors to antiangiogenic therapy and prolong its efficacy, and conversely, antiangiogenic therapy can improve anti–PD-L1 treatment specifically when it generates intratumoral HEVs that facilitate enhanced CTL infiltration, activity, and tumor cell destruction.

Metastatic Colorectal Cancer: Role of Target Therapies and Future Perspectives

2018 ◽  
Vol 18 (5) ◽  
pp. 421-429 ◽  
Author(s):  
Anna Nappi ◽  
Massimiliano Berretta ◽  
Carmela Romano ◽  
Salvatore Tafuto ◽  
Antonino Cassata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Clinical Responses ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Today, we are experiencing a real cultural revolution in the therapeutic approach to cancer of the colon - rectum, that by orphan disease, it is now becoming an important paradigm of scientific innovations and concepts. Survival of patients with metastatic colorectal cancer (m-CRC) has been significantly improved with the introduction of the monoclonal antibodies that have as target the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). The PD-1/PD-L1 pathway in cancer is implicated in tumors escaping immune destruction. This pathway is up -regulated in many tumours. Blockade of this pathway with anti-PD-1 and anti-PD-L1 agents has led to remarkable clinical responses in patients affected by many different types of cancer. The aim of this review is to evaluate the effects of addiction of biological agents to standard chemotherapy in the treatment of m-CRC. We can say that, among the various treatment options, the challenge of the future will be a better selection of the population, to ensure the best possible benefit from treatment with anti-VEGF drugs or anti-EGFR and a careful and customized planning of the therapeutic strategy for each patient.

Fortgeschrittenes medulläres Schilddrüsenkarzinom: Vandetanib verbessert das progressionsfreie Überleben

2012 ◽  
Vol 03 (02) ◽  
pp. 93-92
Author(s):  
Alexander Kretzschmar
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Medulläres Schilddrüsenkarzinom ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Vandetanib ist ein oraler Hemmer des RET-Kinase-, VEGF (Vascular Endothelial Growth Factor Receptor)- und EGFR (Epidermal Growth Factor Receptor)-Signalwegs. In einer zulassungsrelevanten, randomisierten, doppelblinden, placebokontrollierten Phase- III-Studie verlängerte der Tyrosinkinasehemmer das progressionsfreie Überleben (PFS) signifikant länger als Placebo.

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