Targeted Therapy for Brain Metastases

Davies, Michael A.

doi:10.1016/b978-0-12-397927-8.00005-1

Cited by 14 publications

(9 citation statements)

References 146 publications

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“…3,5 There has been a surge in clinical trials guided by genomics in order to better match patients with effective, targeted cancer treatments. 8 The development of CNS metastases often results in exclusion of patients from clinical trials, 9 particularly phase I trials of many novel therapeutics, mainly due to the known poor prognosis and limited efficacy of systemic therapy for these patients historically. Detailed molecular analyses of metastases across pathologies may help identify new therapeutic targets that can benefit these patients.…”

Section: Introductionmentioning

confidence: 99%

Profiles of brain metastases: Prioritization of therapeutic targets

Ferguson

Zheng

Xiu

et al. 2018

Intl Journal of Cancer

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We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of nonsmall cell lung cancer, breast cancer and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next‐generation sequencing with a targeted 47‐gene panel), protein expression (assayed by immunohistochemistry) and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification and mutations among brain metastases, extracranial metastases and primary tumors. The analyzed population included: 16,999 unmatched primary tumor and/or metastasis samples: 8,178 nonsmall cell lung cancers (5,098 primaries; 2,787 systemic metastases; 293 brain metastases), 7,064 breast cancers (3,496 primaries; 3,469 systemic metastases; 99 brain metastases) and 1,757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). TOP2A expression was increased in brain metastases from all 3 cancers, and brain metastases overexpressed multiple proteins clustering around functions critical to DNA synthesis and repair and implicated in chemotherapy resistance, including RRM1, TS, ERCC1 and TOPO1. cMET was overexpressed in melanoma brain metastases relative to primary skin specimens. Brain metastasis patients may particularly benefit from therapeutic targeting of enzymes associated with DNA synthesis, replication and/or repair.

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Section: Introductionmentioning

confidence: 99%

Profiles of brain metastases: Prioritization of therapeutic targets

Ferguson

Zheng

Xiu

et al. 2018

Intl Journal of Cancer

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“…Selected criteria are integrated into CVI calculations in two variations( agdanavičiute, Kelpšaite, and Soomere). Modification of assessment parameters is also done by [7], [8] to adjust the conditions in the field. Here is the equation used in the calculation of the coastal vulnerability index.…”

Section: Figure 2 Research Locationmentioning

confidence: 99%

“…Land utilization / land use maps are essential to understanding changes in land use classes / land in certain areas and how this helps in increasing or decreasing a region's vulnerability [8], [11], Land utilization data is data released by the district government [4]…”

Section: Land Utilizationmentioning

confidence: 99%

“Assessment of Coastal Vulnerability Index on potential agricultural land - CVI, Banyuwangi Regency”

et al. 2020

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Indonesia is an archipelago country that has the longest coastline after Canada (UNCLOS). Banyuwangi District is a coastal area in Northern Java, which has a very dynamic development because of its location of the capital city that located along the coastal area. The purpose of this study is to assess the degree of coastal vulnerability in Banyuwangi District with the higher level of development. The CVI method (Coastal Vulnarability Index) of evisien sting is used to assess vulnerability. The coastal vulnerability is very low over 8 km, with a 15.4% of coastal length of Banyuwangi District. Low vulnerability occurs in areas that are located in areas close to settlements area, with beaches already experiencing human intervention. The low category is about 12 km long, reaching 23.3% of the existing coastal length in Banyuwangi District. The middle category is about 16 km, equivalent to 30.8% of shoreline. While the high category is about 10 km, equivalent to 19.2% of coastal length. The highest category has a length of 6 km, equivalent to 11.5% of the coastal area of Banyuwangi district.

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“…Nearly 50% of patients with advanced malignant melanoma develop BM, and the prevalence of BM in autopsies of these patients is even higher, at 75%. 100 – 102 Multiple BM in malignant melanoma is associated with a poor prognosis, and survival of these patients is generally 6 months or less following diagnosis. 103 , 104 Historically, WBRT is less utilized in this patient population as the tumor is considered radiation-resistant.…”

Section: Targeted Therapies For Brain Metastases In Melanomamentioning

confidence: 99%

Targeted therapy of brain metastases: latest evidence and clinical implications

Lorenzo

Ahluwalia

2017

Ther Adv Med Oncol

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Brain metastases (BM) occur in 20–40% of patients with cancer and 60–75% of patients with BM become symptomatic. Due to an aging population and advances in the treatment of primary cancers, patients are living longer and are more likely to experience complications from BM. The diagnosis of BM drastically worsens long-term survival rates, with multiple metastases being a poor prognostic factor. Until recently, the mainstay of treatment consisted of stereotactic radiosurgery (SRS), surgical resection, whole brain radiation therapy (WBRT), or a combination of these modalities. Systemic chemotherapy has been felt largely ineffective in the treatment of BM due to the presence of the blood–brain barrier (BBB), which includes efflux pumps on brain capillaries. Over the past decade however, researchers have identified therapeutic agents that are able to cross the BBB. These findings could make a multimodality treatment approach possible, consisting of surgery, radiation, immunotherapy, and targeted therapy, which could lead to better disease control in this patient population and prolong survival. In this review, we discuss present evidence on available targeted therapies and their role in the treatment of BM from primary tumors with the highest prevalence of central nervous system (CNS) involvement, specifically non-small cell lung cancer (NSCLC), breast cancer melanoma, and renal cell carcinoma.

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Targeted Therapy for Brain Metastases

Cited by 14 publications

References 146 publications

Profiles of brain metastases: Prioritization of therapeutic targets

Profiles of brain metastases: Prioritization of therapeutic targets

“Assessment of Coastal Vulnerability Index on potential agricultural land - CVI, Banyuwangi Regency”

Targeted therapy of brain metastases: latest evidence and clinical implications

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