Anti-Angiogenics: Their Value in Lung Cancer Therapy

Abstract

Lung cancer is the second most common cancer and the leading cause of cancer-related deaths. Different targeted therapies and the introduction of immunotherapy have successfully improved outcome for patients with non-small lung cancer (NSCLC). Anti-angiogenic drugs are an essential component in the treatment of NSCLC patients. The vascular endothelial growth factor (VEGF)-A antibody bevacizumab is approved for first-line treatment of advanced-stage patients in combination with platinum-based chemotherapy. Ramucirumab, a VEGF receptor antibody, and nintedanib, an anti-angiogenic multi-tyrosine kinase inhibitor, are approved for second-line treatment in combination with docetaxel. This review provides a summary of pivotal trials with anti-angiogenic drugs in NSCLC in different settings. We give an overview of how to position anti-angiogenic therapy in the current treatment algorithms and highlight future directions. The identification of predictive biomarkers for patient selection could improve the success of anti-angiogenic drugs and represents an important area of research. In addition, novel therapeutic targets including endothelial metabolomic intermediates and cellular components of the tumor microenvironment could lead to the identification of innovative new targets besides the VEGF axis.

The anthelmintic agent oxfendazole inhibits cell growth in non‑small cell lung cancer by suppressing c‑Src activation

“…The current strategies being investigated for NSCLC treatment have focused on new targeted therapies against epidermal growth factor receptor, angiogenesis and immune checkpoints. However, these therapies have exhibited limited benefits for patients with NSCLC (27)(28)(29). Therefore, novel and effective drugs are urgently required to treat NSCLC, and one possible strategy is to utilize previously discovered drugs that are currently used to treat different diseases (14).…”

hiPSCs in cardio-oncology: deciphering the genomics

“…127 Other chemotherapeutics that cause thrombotic events, such as ramucirumab and bevacizumab, were specifically designed to impair angiogenesis in tumour cells, so it is unsurprising that they adversely impact the vascular system. 128 Of interest, almost none of the cancer therapies known to cause either arterial or VTE are reported to cause arrhythmias, suggesting that agents that cause arrhythmia are operating through distinct pathways from those that cause thrombosis. 65 Similarly, only carfilzomib, a proteasome inhibitor, causes both cardiotoxicity and thromboembolism, which suggests that, in general, the mechanisms of cardiac cytotoxicity are distinct from those involved in vascular complications.…”

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“…Among chemotherapeutic agents, angiogenesis inhibitors reduce or slow cancer progression by blocking the nutritional supply that the tumor requires. Ramucirumab, which was relatively newly approved by the United States Food and Drug Administration, binds to the extracellular domain of vascular endothelial growth factor-2 (VEGF-2) with high affinity and selectivity and blocks the binding of multiple VEGF ligands (VEGF-A, VEGF-C, and VEGF-D) to VEGFR-2 [ 1 , 2 ]. Clinically, angiogenesis inhibitors are used alone or in combination with other chemotherapeutic agents.…”