Metastasis has intrigued researchers for more than 100 years. Despite the development of technologies and therapeutic strategies, metastasis is still the major cause of cancer-related death until today. The famous “seed and soil” hypothesis is widely cited and accepted, and it still provides significant instructions in cancer research until today. To our knowledge, there are few reviews that comprehensively and correlatively focus on both the seed and soil factors involved in cancer metastasis; moreover, despite the fact that increasingly underlying mechanisms and concepts have been defined recently, previous perspectives are appealing but may be limited. Hence, we reviewed factors involved in cancer metastasis, including both seed and soil factors. By integrating new concepts with the classic hypothesis, we aim to provide a comprehensive understanding of the “seed and soil” hypothesis and to conceptualize the framework for understanding factors involved in cancer metastasis. Based on a dynamic overview of this field, we also discuss potential implications for future research and clinical therapeutic strategies.

A plethora of previous studies have been focused on the role of indoleamine 2,3-dioxygenase 1 (IDO1) in cancer immunity; however, the alternative way of targeting tryptophan 2,3-dioxygenase (TDO2) in cancer immunotherapy has been largely ignored. In particular, the specific role of TDO2 in breast cancer remains unclear. In the present study, we systematically explored and validated the expression and prognostic value of TDO2 in breast cancer using large-scale transcriptome data. We observed overexpression of TDO2 in many types of cancer tissues compared with adjacent normal tissues. TDO2 overexpression was revealed to be positively correlated with malignancy and tumor grade in breast cancer. TDO2 expression was higher in estrogen-negative breast cancer and triple-negative breast cancer, and it was correlated with worse outcome in breast cancer patients. TDO2 expression was correlated with immune infiltrates and tryptophan metabolism-related genes (IDO1 and kynureninase [KYNU]). Therefore, our results indicated that TDO2 plays a pivotal role in regulating the immune microenvironment and tryptophan metabolism in breast cancer, and it predicts poor prognosis in breast cancer, which suggests that TDO2 might be a promising novel immunotherapy target for breast cancer. Additionally, we established the concept that tryptophan-catabolizing enzymes (IDO1, IDO2, TDO2, and KYNU) may function through co-regulating the immunological microenvironment, and thus immunotherapy targeting IDO1 alone might be insufficient.

Purpose. This investigation seeks to elucidate the potential prognostic significance as well as the clinical utility of the controlling nutritional status (CONUT) score in breast cancer patients. Methods. Breast cancer patients managed in our center between January 2010 and December 2016 were recruited for our study. They comprised 187 patients who did not undergo neoadjuvant chemotherapy and 194 who did. A receiver operating characteristic curve (ROC) was utilized in identifying the ideal cut‐off CONUT value. This cut‐off score was then used to reclassify patients into those with high CONUT scores (≥1) and low CONUT scores (<1). The outcomes were analyzed by statistical methods. Results. Univariate and multivariate Cox regression survival analyses revealed that a CONUT score cut‐off of 1 was able to significantly predict duration of disease‐free survival (DFS) (p < 0.001; hazard ratio [HR]: 3.184; 95% CI: 1.786‐5.677; and p < 0.001; HR: 2.465; 95% CI: 1.642‐3.700) and overall survival (OS) (p < 0.001; HR: 2.326; 95% CI: 1.578‐3.429; and p < 0.001; HR: 2.775; 95% CI: 1.791‐4.300). The mean DFS and OS in those with lower CONUT scores were 41.59 (95% CI: 37.66‐45.51 months) and 77.34 months (95% CI: 71.79‐82.90 months), respectively. On the other hand, the average DFS and OS for all individuals in the raised CONUT score group were 39.18 (95% CI: 34.41‐43.95 months) and 71.30 months (95% CI: 65.47‐77.12 months), respectively. Moreover, Kaplan‐Meier survival analysis revealed that those in the raised CONUT score cohort had remarkably worse DFS and OS survival rates compared to individuals in the low CONUT score cohort (Log‐rank test, DFS: χ² = 12.900, p = 0.0003, and OS: χ² = 16.270, p < 0.0001). Conclusion. The survival times of breast cancer patients may be reliably predicted using the CONUT score. This score is an easy, convenient, readily accessible, and clinically significant means of prognosticating patients with breast cancer.

Tumor occurrence, progression and metastasis depend on the crosstalk between tumor cells and stromal cells and on extrinsic factors outside the tumor microenvironment. Exosomal microRNA (miRNA) not only is involved in communications within the tumor microenvironment but also mediates communications between the extrinsic environment and tumor microenvironment. However, most reviews have been limited to the role of endogenous exosomal miRNA in remodeling the tumor microenvironment. Hence, we herein review the role of endogenous exosomal miRNA in mediating intercellular crosstalk within the tumor microenvironment, inducing the formation of the premetastatic niche. To place our vision outside the microenvironment, we also summarize for the first time the most recent studies regarding how exogenous miRNA derived from milk, plants and microbes influences the tumor microenvironment. Furthermore, to improve the value of exosomal miRNA in cancer research and clinical applications, we also provide some novel ideas for future research based on the comprehensive role of exosomal miRNA in remodeling the tumor microenvironment.

Large cohort studies that estimate the variation in suicide risk among cancer patients, depending on disease type and patient characteristics, are lacking. We aimed to investigate suicide risk among patients with different cancers types in the United States (US) and to identify subsets of patients at particularly high risk. A total of 9,300,812 cases of cancer in the Surveillance, Epidemiology, and End Results (SEER) database that were diagnosed between 1975 and 2016 were included in the study. Standardized mortality ratio (SMR) and absolute excess risk (AER) of suicide were estimated. From the included cases, 14,423 cancer patients were identified as having died by suicide, representing 0.26% of all deaths. We found that cancer patients had a higher risk of suicide compared with the general population, which equated to 0.8 excess deaths per 10,000 person-years. Greater suicide risk was correlated with the following: specific cancer sites, male sex, American Indian/Alaskan Native ancestry, being divorced, being uninsured, distance of metastasis, aged between 60 and 69 at diagnosis, and having a more recent diagnosis. The greatest SMR and AER were found in patients with cancers of the respiratory system, followed by those of the oral cavity and pharynx, myeloma, bones and joints, digestive system, and brain and other nervous system cancers. Suicide risk among cancer patients varies greatly and depends on both disease type and patient characteristics. A tailored clinical management should be considered for patients at a higher risk of suicide. Natural Science Foundation of China.

Breast cancer has become the most common cancer worldwide. Despite the major advances made in the past few decades in the treatment of breast cancer using a combination of chemotherapy, endocrine therapy, and immunotherapy, the genesis, treatment, recurrence, and metastasis of this disease continue to pose significant difficulties. New treatment approaches are therefore urgently required. Zinc is an important trace element that is involved in regulating various enzymatic, metabolic, and cellular processes in the human body. Several studies have shown that abnormal zinc homeostasis can lead to the onset and progression of various diseases, including breast cancer. This review highlights the role played by zinc transporters in pathogenesis, apoptosis, signal transduction, and potential clinical applications in breast cancer. Additionally, the translation of the clinical applications of zinc and associated molecules in breast cancer, as well as the recent developments in the zinc-related drug targets for breast cancer treatment, is discussed. These developments offer novel insights into understanding the concepts and approaches that could be used for the diagnosis and management of breast cancer.