The tumor microenvironment plays a pivotal role in the tumorigenesis, progression, and metastatic spread of many cancers including breast. There is now increasing evidence to support the observations that a bidirectional interplay between breast cancer cells and stromal cells exists within the tumor and the tumor microenvironment both at the primary tumor site and at the metastatic site. This interaction occurs through direct cell to cell contact, or by the release of autocrine or paracrine factors which can activate pro-tumor signaling pathways and modulate tumor behavior. In this review, we will highlight recent advances in our current knowledge about the multiple interactions between breast cancer cells and neighboring cells (fibroblasts, endothelial cells, adipocytes, innate and adaptive immune cells) in the tumor microenvironment that coordinate to regulate metastasis. We also highlight the role of exosomes and circulating tumor cells in facilitating breast cancer metastasis. We discuss some key markers associated with stromal cells in the breast tumor environment and their potential to predict patient survival and guide treatment. Finally, we will provide some brief perspectives on how current technologies may lead to the development of more effective therapies for the clinical management of breast cancer patients.

Breast cancer (BC) is the most common cancer in women, with metastatic BC being responsible for the highest number of deaths. A frequent site for BC metastasis is the brain. Brain metastasis derived from BC involves the cooperation of multiple genetic, epigenetic, angiogenic, and tumor–stroma interactions. Most of these interactions provide a unique opportunity for development of new therapeutic targets. Potentially targetable signaling pathways are Notch, Wnt, and the epidermal growth factor receptors signaling pathways, all of which are linked to driving BC brain metastasis (BCBM). However, a major challenge in treating brain metastasis remains the blood–brain barrier (BBB). This barrier restricts the access of unwanted molecules, cells, and targeted therapies to the brain parenchyma. Moreover, current therapies to treat brain metastases, such as stereotactic radiosurgery and whole-brain radiotherapy, have limited efficacy. Promising new drugs like phosphatase and kinase modulators, as well as BBB disruptors and immunotherapeutic strategies, have shown the potential to ease the disease in preclinical studies, but remain limited by multiple resistance mechanisms. This review summarizes some of the current understanding of the mechanisms involved in BC brain metastasis and highlights current challenges as well as opportunities in strategic designs of potentially successful future therapies.

Chromosomes are organized in distinct nuclear areas designated as chromosome territories (CT). The structural formation of CT is a consequence of chromatin packaging and organization that ultimately affects cell function. Chromosome positioning can identify structural signatures of genomic organization, especially for diseases where changes in gene expression contribute to a given phenotype. The study of CT in hematological diseases revealed chromosome position as an important factor for specific chromosome translocations. In this review, we highlight the history of CT theory, current knowledge on possible clinical applications of CT analysis, and the impact of CT in the development of hematological neoplasia such as multiple myeloma, leukemia, and lymphomas. Accumulating data on nuclear architecture in cancer allow one to propose the three-dimensional nuclear genomic landscape as a novel cancer biomarker for the future.

A taxa de mortalidade (TM) representa um dos principais indicadores da qualidade da assistência a pessoa com câncer de mama (CM), mostrando-se como um instrumento fundamental no delineamento e revisão das políticas voltadas à pessoa acometida pela doença. A abordagem terapêutica, por sua vez, representa um dos eixos primordiais à redução da mortalidade pela doença. Assim, o objetivo deste estudo é caracterizar o perfil da mortalidade por CM no Brasil, bem como propor uma nova alternativa terapêutica, baseada no uso de produtos naturais. Para isso, realizou-se um estudo documental-retrospectivo, descrevendo a distribuição da TM por CM no Brasil, durante o período de 1987 a 2016, considerando fatores como sexo e faixa etária; em consonância, também foi realizado um estudo experimental, de caráter quanti-qualitativo, para avaliar o potencial citotóxico da (S)-(+) carvona e da (R)-(-)-carvona em linhagens celulares de CM. Assim, constatou-se que a TM por CM no Brasil apresenta uma tendência crescente ao longo dos anos, independe de sexo e faixa etária. No entanto, observou-se que no sexo feminino houve um maior número de mortes e, no sexo masculino, uma maior progressão da TM ao longo dos anos. Ademais, a amplificação da mortalidade por CM ocorreu em conformidade com o aumento da idade, revelando uma relação de proporcionalidade entre esses dois fatores. Com relação à análise experimental, constatou-se que tanto a (S)-(+) carvona como a (R)-(-)-carvona revelaram-se citotóxicas às linhagens celulares de CM, apresentando um efeito dependente da concentração.

Purpose of Review: Pancreatic ductal adenocarcinoma remains among the deadliest malignancies worldwide, and effective therapies are still lacking. Actinomycetota are among the richest microbial sources of bioactive secondary metabolites, and three agents in clinical use against pancreatic malignancy derive from them — streptozotocin, everolimus and doxorubicin — though all three are indicated for neuroendocrine rather than ductal tumors. This review provides a critical narrative synthesis of Actinomycetota-derived metabolites evaluated in pancreatic cancer models, with every potency value re-derived from the primary literature and interpreted alongside assay conditions and available mechanistic and in vivo evidence. Recent Findings: Fifty-two compounds from 25 primary reports encompass polyketides, nonribosomal peptides, depsipeptides, RiPPs, alkaloids, ionophores and hybrid scaffolds. Rather than a simple ranking of increasingly potent cytotoxins, the literature poses a sharper question about selectivity. Two compounds are conditionally active: kigamicin D only under nutrient deprivation and BE-43547A ₂ only under hypoxia, exploiting the metabolic state that defines the disease rather than any intrinsic difference between malignant and normal cells. Both were recovered by screens built to detect that behavior, and neither has been shown to hold a therapeutic window in vivo. Separately, thiogochangamide B retains activity in gemcitabine-resistant models, while trienomycin A binds STAT3 directly, suppresses proliferation across eight pancreatic lines, achieves 84–98% tumor growth inhibition in xenografts at doses producing no detectable toxicity, and distributes preferentially to pancreatic tissue. Summary: Conditional activity is best read as a hypothesis about how such compounds should be sought rather than as an established route to selectivity. Despite remarkable chemical diversity, translation remains constrained by the limited use of normal-cell controls, predictive biomarkers and clinically relevant preclinical models. Screens conducted in nutrient-replete, normoxic monolayer culture will systematically miss compounds of this kind. Future efforts should prioritize compounds that exploit the metabolic liabilities of pancreatic cancer rather than pursuing greater cytotoxic potency.