Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Abstract
Brain metastases (BM) occur in 20% to 40% of patients with cancer and result in significant morbidity and poor survival. The main therapeutic options include surgery, whole brain radiotherapy, stereotactic radiosurgery and chemotherapy. Although significant progress has been made in diagnostic and therapeutic methods, the prognosis in these patients remains poor. Furthermore, the poor penetrability of chemotherapy agents through the blood brain barrier (BBB) continues to pose a challenge in the management of this disease. Preclinical evidence suggests that new targeted treatments can improve local tumor control but our clinical experience with these agents remains limited. In addition, several clinical studies with these novel agents have produced disappointing results. This review will examine the knowledge of targeted therapies in BM. The preclinical and clinical evidence of their use in BM induced by breast cancer, non-small cell lung cancer and melanoma will be presented. In addition, we will discuss the role of antiangiogenic and radiosensitising agents in the treatment of BM and the current strategies available to increase BBB permeability. A better understanding of the mechanism of action of these agents will help us to identify the best targets for testing in future clinical studies.

Biology of brain metastases and novel targeted therapies: Time to translate the research (PDF Download Available). Available from: https://www.researchgate.net/publicatio ... e_research [accessed Aug 22, 2017].



https://www.researchgate.net/publicatio ... e_research

This is part of the introduction-
2.1 The biology of brain metastases, paragraph 2-

"Different theories have been developed to explain the pathogene-sis of metastatic spread. James Ewing suggested that the differentpatterns of blood circulation that connect the primary tumor withthe secondary organs can explain the organ-specific propensity ofmetastatic spread [30]. Similar to the metastatic process in other or-gans, certain tumors present a tropism for metastatic spread to thebrain. Over a century ago, Stephen Paget hypothesized that tumorspresent an organ-specific metastatic pattern that depends on theaffinity of tumor cell (seed) for the tumor microenvironment (soil)and it probably involves several inherent biological factors [31]. Fidlerand colleagues tested the seed and soil hypothesis of Paget in murinemodels by injecting melanoma cells into internal and external carotidarteries [32–34]. In support of the theory, B16v melanoma cells me-tastasized exclusively to ventricles and meninges of the mice whileK-1735 melanoma cells only spread to brain parenchyma, indepen-dently of their injection site, indicating a specific pattern of metastaticspread that cannot be explained only by the anatomical distributionof blood vessels [27,32,33]. Interestingly, a preclinical study has pre-viously shown that cancer cells can, in certain conditions, bring com-ponents of the tumor microenvironment (soil), such as activatedfibroblasts, to the sites of secondary spread

Biology of brain metastases and novel targeted therapies: Time to translate the research (PDF Download Available). Available from: https://www.researchgate.net/publicatio ... e_research [accessed Aug 22, 2017].

I find the spread from lung to brain, quite interesting

See
2.2. Hematogenous spread of cancer cell

"2.2. Hematogenous spread of cancer cellsUpon intravasation, tumor cells arrest at vascular branch points ofthe capillary bed with slow blood flow [25]. Previous reports haveshown that tumor cells that metastasize to CNS likely enter thebrain parenchyma through the arterial blood supply. Indeed, the ma-jority of brain metastases induced by lung cancer, breast cancer andmelanoma occur at the junctions between gray and white matterand at the border of craniospinal fluid-circulating areas that are sup-plied by inctracranial arteries [38]. Retroperitoneal malignanciesoften lead to the formation of BM at the posterior cranial fossawhich could manifest through retrograde dissemination via thevenous plexus of Batson [7,39]. In contrast to other organs, the brainlacks lymphatic circulation and lymph nodes [40].In addition, the viability of circulating metastatic cancer cells ishigher when primary tumor cells are associated with stromal cellssuch as fibroblasts from the primary tumor. Duda et al. has demon-strated that co-traveling fibroblast provide a growth advantagefor metastases induced by lung cancer and patients with BM oftencontain carcinoma-associated fibroblast, in contrast to primary brain tumor."

Biology of brain metastases and novel targeted therapies: Time to translate the research (PDF Download Available). Available from: https://www.researchgate.net/publicatio ... e_research [accessed Aug 22, 2017].