The Journey of Cancer Cells to the Brain: Challenges and Opportunities

Abstract

Cancer metastases into the brain constitute one of the most severe, but not uncommon, manifestations of cancer progression. Several factors control how cancer cells interact with the brain to establish metastasis. These factors include mediators of signaling pathways participating in migration, infiltration of the blood–brain barrier, interaction with host cells (e.g., neurons, astrocytes), and the immune system. Development of novel therapies offers a glimpse of hope for increasing the diminutive life expectancy currently forecasted for patients suffering from brain metastasis. However, applying these treatment strategies has not been sufficiently effective. Therefore, there is a need for a better understanding of the metastasis process to uncover novel therapeutic targets. In this review, we follow the journey of various cancer cells from their primary location through the diverse processes that they undergo to colonize the brain. These processes include EMT, intravasation, extravasation, and infiltration of the blood–brain barrier, ending up with colonization and angiogenesis. In each phase, we focus on the pathways engaging molecules that potentially could be drug target candidates.

Diabetes Mellitus Is a Strong Independent Negative Prognostic Factor in Patients with Brain Metastases Treated with Radiotherapy

“…The formation of BM depends on the extravasation of tumor cells, perivascular tumor cell growth, and the co-option of pre-existing vessels in a complex multistep process [33][34][35]. In addition, cerebral perfusion and oxygenation are crucial for the effect of local radiotherapy on BM [36,37], and alterations in cerebral perfusion could also modulate the efficacy of systemic treatment [38,39].…”

Brain‐Decellularized ECM‐Based 3D Myeloid Sarcoma Platform: Mimicking Adaptive Phenotypic Alterations in the Brain

“…Chronic myeloid leukemia (CML) is caused by a genetic mutation in immature hematopoietic stem cells (HSCs) in the bone (TKIs), which may be effective during the chronic phase of CML, further complicating treatment efforts. [7] An in-depth understanding of the phenotypic changes in CML cells as they form masses in the brain is essential for devising efficient and personalized therapeutic strategies for intracranial MS. [6] The interaction between the extracellular matrix (ECM), the surrounding brain cells, and lower oxygen tension are distinctive external factors that influence intracranial MS compared to factors that influence blood-circulating CML cells. [4b,8] CML cells may undergo genetic and epigenetic changes to adapt to the new brain environment, which can influence cellular morphology, cell cycle, differentiation, metabolic activity, and drug sensitivity.…”

“…[ 5 ] The prognosis of patients with intracranial MS is particularly poor because of the limited penetration of cytostatic drugs for the treatment of leukemia across the blood–brain barrier, creating a challenging treatment environment. [ 6 ] Furthermore, these masses often develop resistance to therapies such as tyrosine kinase inhibitors (TKIs), which may be effective during the chronic phase of CML, further complicating treatment efforts. [ 7 ] An in‐depth understanding of the phenotypic changes in CML cells as they form masses in the brain is essential for devising efficient and personalized therapeutic strategies for intracranial MS. [ 6 ]…”

“…[ 6 ] Furthermore, these masses often develop resistance to therapies such as tyrosine kinase inhibitors (TKIs), which may be effective during the chronic phase of CML, further complicating treatment efforts. [ 7 ] An in‐depth understanding of the phenotypic changes in CML cells as they form masses in the brain is essential for devising efficient and personalized therapeutic strategies for intracranial MS. [ 6 ]…”

A Convolution-Based AI Neural Network Achieves 90% Accuracy in Predicting Cancer Type Based on Copy Number Alterations

“…Cancer, with its metastatic nature, stands as a formidable force shaping life expectancy [1]. Metastasis, the insidious spread of cancer cells to distant sites, poses a dire threat to patients, setting the boundaries of treatment efficacy [2].…”