VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside

Arjaans, Marlous; Schröder, Carolina P.; Oosting, Sjoukje F.; Dafni, Urania; Kleibeuker, J.E.; Vries, Elisabeth G.E. de

doi:10.18632/oncotarget.6918

Cited by 92 publications

(79 citation statements)

References 91 publications

(97 reference statements)

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“…In this regard, it is well established that bevacizumab treatment can induce normalization of the tumor vasculature, an effect suggested to result in reduced interstitial pressures and improved drug delivery [80]. However, additional preclinical and clinical data have emerged consistent with reduced tumor uptake of both chemotherapeutic drugs and antibodies following antiangiogenic therapy (reviewed in [81]). The initial findings from the dose-escalation stage of FORWARD II were presented at the ASCO Annual Meeting in 2017 [82].…”

Section: Combinatorial Strategies For the Treatment Of Platinum-resismentioning

confidence: 99%

A Review of Mirvetuximab Soravtansine in the Treatment of Platinum-Resistant Ovarian Cancer

et al. 2017

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Resistance to platinum-based therapy poses a significant clinical challenge for the management of advanced ovarian cancer, a leading cause of cancer mortality among women. Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-α, a validated molecular target for therapeutic intervention in this disease. Here, we examine mirvetuximab soravtansine's mechanism of action and pharmacology, and review its clinical evaluation in ovarian cancer to date. We focus on the favorable tolerability and encouraging signals of efficacy that have emerged, most notably in patients with platinum-resistant disease. Ongoing Phase III monotherapy and Phase Ib/II combination trials evaluating its activity in the setting of platinum resistance are emphasized, which will help define its role in the evolving landscape of ovarian cancer therapy. Ovarian cancer landscapeOvarian cancer remains a leading cause of gynecological cancer mortality, responsible for 152,000 deaths annually worldwide [1]. In the USA alone, it is estimated that 22,440 women will be diagnosed with ovarian cancer in 2017 and more than 14,000 will die due to this disease [2]. The remarkable degree of cellular and molecular heterogeneity exhibited by tumors of the ovary (including those arising from the fallopian tubes and primary peritoneum) is such that ovarian cancer is no longer considered a single disease entity with variable morphology, but rather a collection of neoplasms each associated with their own distinct histological subtypes and response to therapy [3,4]. Among these, epithelial ovarian cancer (EOC) accounts for approximately 95% of ovarian cancer malignancies [5,6]. The foundation of current standard-of-care treatment for women diagnosed with EOC is cytoreductive (debulking) surgery and chemotherapy using a platinum-based combination regimen, most commonly the carboplatin-paclitaxel doublet. This strategy has largely reached a plateau of effectiveness in improving overall patient survival [7,8]. The continuing high mortality is associated, at least in part, with the fact that EOC is overwhelmingly diagnosed at an advanced stage. Furthermore, while EOC is highly chemosensitive and most individuals achieve remission with front-line therapy, up to 80% of patients relapse and require further treatment without the expectation of cure [9].The development of platinum resistance in EOC appears to be a dynamic and multifactorial process, although the underlying molecular mechanisms remain poorly defined [10,11]. Recurrent EOC is classified based on the length Drug Evaluation Moore, Martin, O'Malley et al. of time, empirically divided into 6-month blocks, since receiving treatment with a platinum agent, known as the platinum-free interval [7,12]. The classification is as follows:r Refractory: progression during or within 4 weeks of platinum-based chemotherapy; r Primary resistant: relapse within 6 months of completing initial platinum therapy; r Partially platinum sensitive: relapse between 6 and 12 months; r Platinum sensitiv...

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Section: Combinatorial Strategies For the Treatment Of Platinum-resismentioning

confidence: 99%

A Review of Mirvetuximab Soravtansine in the Treatment of Platinum-Resistant Ovarian Cancer

et al. 2017

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“…Vascular endothelial growth factors are key players in the process of tumour angiogenesis, and the VEGF pathway has therefore been an important focus for anticancer drug development [12] . After the first VEGF-targeted agent, the antiVEGF monoclonal antibody bevacizumab (Avastin, Genentech), showing clinical benefit in patients with metastatic CRC when combined with chemotherapy, the studies about angiogenic process has continued to increase [13] .…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Antiangiogenic and Antimetastatic Effects of Penicillium chrysogenum Secondary Metabolites

Dikmen¹

2017

ijps

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Dikmen, et al.: Antiangiogenic and Antimetastatic Effects of Penicillium chrysogenumDevelopment of resistance to standard therapy and toxic side effects are the major challenges encountered in chemotherapy of colorectal cancer. Increasing evidence has shown the ability of natural products to overcome various challenging disorders. Since, the development of antibiotics, fungi have been shown to be a wide useful source of lead compounds for the development of new pharmaceuticals. Fungal secondary metabolites from extreme environments are remarkable due to their diverse components, which makes them interesting candidates for drug discovery. In order to discover novel active antimetastatic and antiangiogenic compounds, secondary metabolites of halotolerant Penicillium chrysogenum-1 isolated from Tuz Lake in Turkey and ethyl acetate extract of halotolerant P. chrysogenum-1 was prepared from the isolate of halotolerant P. chrysogenum-1 culture medium. Firstly, antioxidant activity of the extract was determined. Then cytotoxicity and cell proliferation were investigated by WST-1 assay and real-time cell analysis system-DP on human umbilical vein endothelial cells and colorectal carcinoma cells, respectively. Antiangiogenic effects on human umbilical vein endothelial cells were evaluated with cell migration and invasion assays by using real-time cell analysis system. Also, mRNA expression levels of metastasis and angiogenesis-related genes, VEGFA, VEGFB, EGFR, COX-10, ANGPT-1 and IL-8 were determined on both cell lines. Results indicated that halotolerant P. chrysogenum-1 extract exhibited significant antimetastatic and antiangiogenic effects. According to the real-time cell analysis system results, IC 50 concentrations of halotolerant P. chrysogenum-1 extract on Caco-2 and human umbilical vein endothelial cells were calculated as 55.2 and 37.89 µg/ml, respectively for 72 h. These results indicated that the secondary metabolites of halotolerant P. chrysogenum-1 extract could have the potential as a preventive and therapeutic agent in metastatic cancer processes.

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“…It has been approved for the treatment of metastatic colon cancer and metastatic kidney cancer as well as non-small cell lung cancer and glioblastoma. Due to the antiangiogenic mechanism of this agent it may reduce wound healing and should not be used soon after surgery (20)(21)(22); (iii) Panitumumab which is a human IgG2 kappa MAB is used to eradicate metastatic colon cancer expressing epidermal growth factor receptor (EGFR) which has been unresponsive to traditional chemotherapy (23)(24)(25); (iv) Cetuximab a human/mouse chimeric MAB, which also binds to and inactivates the EGFR, is used in the treatment of EGFR-positive colon cancer and also for head and neck cancers (24)(25)(26); (v) Ofatumumab is a human IgG1 MAB used in patients with chronic lymphocytic leukemia who are unresponsive to chemotherapy (27)(28)(29)(30) ; (vi) Trastuzumab is a humanized MAB that acts at extracellular HER-2/neu which impedes ERGR activity. This agent is used in patients with HER-2/neu-positive breast cancer and metastatic gastrointestinal (GI) cancers and in patients with other forms of cancer that express HER-2/neu (31-34); (vii) Rituximab is a human/murine MAB that has been approved for the treatment of non-Hodgkin's lymphoma and also lymphocytic leukemia.…”

Section: Antitumor Monoclonal Antibodies (Mabs)mentioning

confidence: 99%

Monoclonal Antibodies for the Treatment of Cancer

Pento

2017

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Abstract.Cancer metastasis is responsible for most of the morbidity and mortality associated with cancer. Cancer metastatic progression is a multiple step process which includes enhanced cell proliferation, release of proteolytic enzymes, cell motility and invasion, angiogenesis and establishment of a supportive microenvironment at the sites of metastatic growth (1, 2).Traditional cancer therapy has focused on removal or destruction of tumour cells by surgery, radiation and rather nonselective types of chemotherapy. Surgery and radiation are often effective with tumours which are localized and have not metastasized to multiple sites throughout the body. Chemotherapy appears to be most effective in the treatment of metastatic cancer; however, typical chemotherapeutic agents such as cisplatin, methotrexate, vincristine, 5-fluorouracil among many others, focus on rapidly growing tissues since cancer cells are relatively rapidly growing. Thus, cancer chemotherapy often results in a high incidence of unwanted and damaging side-effects in rapidly-dividing normal tissues, such as blood cells and cells lining gastrointestinal tract.With a greater understanding of cellular chemistry and genomics during the past twenty years, cellular targets that are unique to cancer cells have been identified and chemotherapeutic agents which specifically bind to, destroy or otherwise inactivate these unique cellular targets have been developed. These agents which impede these unique or overexpressed cancer targets tend to be more selective, -thus more effective with fewer side-effects than traditional, nonselective chemotherapy. They target critical checkpoints which are often overexpressed on rapidly growing and malignant cancer cells, such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and tyrosine kinase. Therefore, cancer Immunotherapy is an exciting and relatively new method to selectively block critical checkpoints in the process of cancer development (3, 4).

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VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside

Cited by 92 publications

References 91 publications

A Review of Mirvetuximab Soravtansine in the Treatment of Platinum-Resistant Ovarian Cancer

A Review of Mirvetuximab Soravtansine in the Treatment of Platinum-Resistant Ovarian Cancer

Evaluation of Antiangiogenic and Antimetastatic Effects of Penicillium chrysogenum Secondary Metabolites

Monoclonal Antibodies for the Treatment of Cancer

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