Current approaches to the treatment of metastatic brain tumours

Owonikoko, Taofeek K.; Arbiser, Jack L.; Zelnak, Amelia; Shu, Hui; Shim, Hyunsuk; Robin, Adam; Kalkanis, Steven N.; Whitsett, Timothy G.; Salhia, Bodour; Tran, Nhan L.; Ryken, Timothy C.; Moore, Michael K.; Egan, Kathleen M.; Olson, Jeffrey J.

doi:10.1038/nrclinonc.2014.25

Cited by 245 publications

(184 citation statements)

References 204 publications

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“…For example, VEGF-B may significantly contribute to development of retinopathy of prematurity in human infants and in solid cancers where hypoxia in the tumor microenvironment undergoes constant changes. Another extended clinical implication of our findings is that VEGF-B might play a role in brain tumor development and invasion as seen in other systems (39)(40)(41). These interesting clinically related issues coupled to VEGF-B warrant future investigation.…”

Section: Discussionmentioning

confidence: 97%

VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish

Jensen

Nakamura

Bräutigam

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Physiological functions of vascular endothelial growth factor (VEGF)-B remain an enigma, and deletion of the Vegfb gene in mice lacks an overt phenotype. Here we show that knockdown of Vegfba, but not Vegfbb, in zebrafish embryos by specific morpholinos produced a lethal phenotype owing to vascular and neuronal defects in the brain. Vegfba morpholinos also markedly prevented development of hyaloid vasculatures in the retina, but had little effects on peripheral vascular development. Consistent with phenotypic defects, Vegfba, but not Vegfaa, mRNA was primarily expressed in the brain of developing zebrafish embryos. Interestingly, in situ detection of Neuropilin1 (Nrp1) mRNA showed an overlapping expression pattern with Vegfba, and knockdown of Nrp1 produced a nearly identically lethal phenotype as Vegfba knockdown. Furthermore, zebrafish VEGF-Ba protein directly bound to NRP1. Importantly, gain-of-function by exogenous delivery of mRNAs coding for NRP1-binding ligands VEGF-B or VEGF-A to the zebrafish embryos rescued the lethal phenotype by normalizing vascular development. Similarly, exposure of zebrafish embryos to hypoxia also rescued the Vegfba morpholino-induced vascular defects in the brain by increasing VEGF-A expression. Independent evidence of VEGF-A gain-of-function was provided by using a functionally defective Vhl-mutant zebrafish strain, which again rescued the Vegfba morpholino-induced vascular defects. These findings show that VEGF-B is spatiotemporally required for vascular development in zebrafish embryos and that NRP1, but not VEGFR1, mediates the essential signaling.

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Section: Discussionmentioning

confidence: 97%

VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish

Jensen

Nakamura

Bräutigam

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The median overall survival (OS) rate of these patients with brain metastases is <1 year (3). Current therapeutic approaches for cancer bone and brain metastasis include palliative radiotherapy and systemic therapy with chemotherapy and targeted agents (3,4). Platinum-based combination chemotherapy is the standard of care for non-small cell lung cancer (NSCLC) (5); however, drug resistance limits the therapeutic efficacy of combination chemotherapy in advanced NSCLC (6).…”

Section: Introductionmentioning

confidence: 99%

Palliative treatment efficacy of glucose inhibition combined with chemotherapy for non‑small cell lung cancer with widespread bone and brain metastases: A case report

et al. 2017

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Abstract. Otto Warburg observed in 1924 that cancer cells were dependent exclusively on glycolysis for the production of energy even in the presence of oxygen (the 'Warburg effect'). Consequently, cancer cells require ~19 times more glucose uptake to obtain equivalent amounts of energy as normal cells. The Warburg effect is the scientific basis for positron emission tomography (PET), which has markedly improved cancer detection. During chemotherapy, cancer cells may upregulate their expression of multi-drug resistance proteins and ultimately cause treatment failure. As multi-drug resistance proteins require energy to operate, the present report evaluated the potential clinical efficacy of lowering blood glucose with insulin during chemotherapy for a patient with advanced pulmonary adenocarcinoma with multiple metastases. A 64-year-old male was admitted to the Department of Medical Oncology at Changzhou Tumor Hospital (Changzhou, China) due to an irritating cough and multiple bone pain. PET/computed tomography (CT) with F-18 fluorodeoxy glucose ( 18 F-FDG) identified multiple hypermetabolic foci in the right hilum, right upper lung, shoulder blades, thoracic vertebrae, lumbar, sacrum, bilateral iliac crest and pelvis. Additionally, magnetic resonance imaging detected multiple metastases in the brain. The patient received 56 repeat treatments with insulin to induce hypoglycemia combined with reduced doses of chemotherapy over an 8-month period. For each treatment, insulin at 0.2 U/kg body weight was injected intravenously (i.v.), and when blood glucose level reached 2.5-3.0 mmol/l, navelbine (10 mg), cisplatin (10 mg) and fluorouracil (250 mg) were injected (i.v.) over a period of ~10 min. The patient's blood glucose level was returned to normal immediately after chemotherapy with an i.v. injection of 20 ml 50% glucose solution. During the 8-month chemotherapy regimen, the patient received two PET/CT follow-ups. The results demonstrated that the levels of 18 F-FDG uptake in all lesions had been reduced. In addition, the patient exhibited improved appetite and weight gain, a reduced cough, and had less pain. The levels of tumor markers, namely carcinoembryonic antigen, carcinoma antigen 15-3, CYRA21-1, neuron-specific enolase, also declined gradually. These results suggest that controlled, mild hypoglycemia may be safely combined with low dose chemotherapy to provide clinical benefit for advanced non-small cell lung cancer. IntroductionAmong patients with lung cancer, 30-40% develop bone metastases (1), while 40-50% develop brain metastases (2,3). The median overall survival (OS) rate of these patients with brain metastases is <1 year (3). Current therapeutic approaches for cancer bone and brain metastasis include palliative radiotherapy and systemic therapy with chemotherapy and targeted agents (3,4). Platinum-based combination chemotherapy is the standard of care for non-small cell lung cancer (NSCLC) (5); however, drug resistance limits the therapeutic efficacy of combination chemotherapy in advanced NSCLC (6)....

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“…For patients with brain metastases from lung cancer, the median survival time is one to two months if they are not treated or best support treated [4]. The survival time of patients can be prolonged through treatment [5][6]. Radiotherapy is the major and effective treatment for multiple brain metastases, and the whole brain radiotherapy (WBRT) is the standard treatment for multiple brain metastases, while radiotherapy has side-effect on patients' life quality.…”

Section: Introductionmentioning

confidence: 99%

Clinical study of the treatment of multiple brain metastases from adenocarcinoma of the lung by simultaneous integrated boost intensity-modulated radiotherapy

Shao¹,

S²,

Wang³

et al. 2018

J Cancer Res Ther.

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Objective: To investigate the effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB) and sequential boost conformal radiotherapy (CRT) in treatment of multiple brain metastases from lung adenocarcinoma. Methods: Forty-two patients with multiple brain metastases from lung adenocarcinoma were analyzed. The epidermal growth factor (EGFR) mutations were negative, ECOG (Eastern Cooperative Oncology Group) were not more than two, the diameters of brain metastases were from 0.5cm to 3.0cm and the numbers of brain metastases were from three to five. The target volume of radiotherapy included whole brain and brain metastatic tumor. The radiation models were divided into SIB in 26 cases and CRT in 16 cases. The median radiation dose of whole brains in SIB and CRT groups were 40Gy, and the brain metastases tumor were 55Gy, 60Gy respectively, and the median number of radiotherapy for 22 times, 30 times. Thirty one patients followed by pemetrexed maintenance chemotherapy (PMC) or docetaxel maintenance chemotherapy (DMC) and 11 patients received no maintenance chemotherapy (NMC). Results: The 1-, 3-, and 5-year survival rates of whole group were 92.8%, 23.8%, and 4.8%, respectively. The median survival time of SIB and CRT groups were 36 months, 29 months, respectively. The SIB group was better than CRT group, and PMC was better than DMC or NMC. Multiple factors analyses showed ECOG, dose and times of brain metastatic tumor radiotherapy, and cycles of PMC were independent risk factors for survival time. The late main adverse reaction was hypomnesia. Conclusion: SIB was superior to CRT, and PMC could improve survival time.

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Current approaches to the treatment of metastatic brain tumours

Cited by 245 publications

References 204 publications

VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish

VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish

Palliative treatment efficacy of glucose inhibition combined with chemotherapy for non‑small cell lung cancer with widespread bone and brain metastases: A case report

Clinical study of the treatment of multiple brain metastases from adenocarcinoma of the lung by simultaneous integrated boost intensity-modulated radiotherapy

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