Cancer and Metastasis Reviews最新文献

The intersection of HIV and melanoma presents a complex and unique challenge, marked by distinct patterns in incidence, mortality, and treatment response. Higher mortality rates among people with HIV who develop melanoma underscore an urgent need to identify the factors influencing these outcomes. Investigating immune system dynamics, the effects of anti-retroviral drugs, and the evolving landscape of cancer immunotherapy in this population holds promise for new insights, though significant uncertainties remain. Over the past 25 years, melanoma research has demonstrated that a robust immune response is critical for effective treatment. In the context of chronic HIV infection, viral reservoirs enable the virus to persist despite anti-retroviral therapy and foster dysregulated myeloid and T cell compartments. The resulting chronic inflammation weakens the immune system and damages tissues, potentially creating "cold" tumor microenvironments that are less responsive to therapy. In this challenging context, animal models become invaluable for uncovering underlying biological mechanisms. While these models do not fully replicate human HIV infection, they provide essential insights into critical questions and inform the development of tailored treatments for this patient population. Clinically, increasing trial participation and creating a centralized, accessible repository for HIV and cancer samples and data are vital. Achieving these goals requires institutions to address barriers to research participation among people with HIV, focusing on patient-centered initiatives that leverage biomedical research to improve their outcomes and extend their lives.

Osteosarcoma is the most common malignant bone tumor, primarily affecting children and young adults. For these young patients, the current treatment options for osteosarcoma impose considerable constraints on daily life with significant morbidity and a low survival rate. Despite ongoing research efforts, the 5-year survival rate of first-diagnosed patients without metastases has not changed in the past four decades. The demand for novel treatments is currently still unmet, in particular for effective second-line therapy. Therefore, there is an urgent need for advanced preclinical models and drug-testing platforms that take into account the complex disease characteristics, the high heterogeneity of the tumour and the interactions with the bone microenvironment. In this review, we provide a comprehensive overview about state-of-the-art tissue-engineered and patient-specific models for osteosarcoma. These sophisticated platforms for advanced therapy trials aim to improve treatment outcomes for future patients by modelling the patient's disease state in a more accurate and complex way, thus improving the quality of preclinical research studies.

Breast cancer remains one of the leading causes of death in women around the world. A majority of deaths from breast cancer occur due to cancer cells colonizing distant organ sites. When colonizing these distant organ sites, breast cancer cells have been known to enter into a state of dormancy for extended periods of time. However, the mechanisms that promote dormancy as well as dormant-to-proliferative switch are not fully understood. The tumor microenvironment plays a key role in mediating cancer cell phenotype including regulation of the dormant state. In this review, we highlight cell-cell interactions in the tumor microenvironment mediating breast cancer dormancy at the primary and metastatic sites. Specifically, we describe how immune cells from the lymphoid lineage, tumor-associated myeloid lineage cells, and stromal cells of non-hematopoietic origin as well as tissue resident stromal cells impact dormancy vs. proliferation in breast cancer cells as well as the associated mechanisms. In addition, we highlight the importance of developing model systems and the associated considerations that will be critical in unraveling the mechanisms that promote primary and metastatic breast cancer dormancy mediated via cell-cell interactions.

Small cell lung cancer (SCLC) represents an aggressive neuroendocrine (NE) tumor within the pulmonary region, characterized by very poor prognoses. Druggable targets for SCLC remain limited, thereby constraining treatment options available to patients. Immuno-chemotherapy has emerged as a pivotal therapeutic strategy for extensive-stage SCLC (ES-SCLC), yet it fails to confer significant efficacy in cases involving liver metastases (LMs) originating from SCLC. Therefore, our attention is directed towards the challenging subset of SCLC patients with LMs. Disease progression of LM-SCLC patients is affected by various factors in the tumor microenvironment (TME), including immune cells, blood vessels, inflammatory mediators, metabolites, and NE substances. Beyond standard immuno-chemotherapy, ongoing efforts to manage LMs in SCLC encompass anti-angiogenic therapy, radiotherapy, microwave ablation (MWA) / radiofrequency ablation (RFA), trans-arterial chemoembolization (TACE), and systemic therapies in conjunction with local interventions. Prospective experimental and clinical investigations into SCLC should prioritize precise and individualized approaches to enhance the prognosis across distinct patient cohorts.

Tumor metastasis is the primary cause of cancer-related mortality and remains a major hurdle in cancer treatment. Traditional cigarette smoking has been extensively studied for its role in promoting metastasis. However, the impact of e-cigarette (e-cig) on cancer metastasis is not well understood despite their increasing popularity as a supposedly safer alternative. This mini review synthesizes current literature on the effects of e-cig on cancer metastasis, focusing on the processes of dissemination, dormancy, and colonization. It also incorporates recent findings from our laboratory regarding the role of e-cig in tumor progression. E-cig exposure enhances metastatic potential through various mechanisms: it induces epithelial-mesenchymal transition (EMT), increasing cell migratory and invasive capabilities; promotes lymphangiogenesis, aiding tumor cell spread; and alters the pre-metastatic niche to support dormant tumor cells, enhancing their reactivation and colonization. Furthermore, e-cig induce significant epigenetic changes, such as DNA methylation and histone modifications, which regulate genes involved in metastasis. Our data suggest that e-cig upregulate histone demethylases like KDM6B in macrophages, impacting the TME and promoting metastasis. These findings underscore the need for further research to understand the long-term health implications of e-cig use and inform public health policies to reduce e-cig use.

Kinesin-like protein 18A (KIF18A) is a member of the kinesin family of molecular motor proteins, which utilise energy from the hydrolysis of adenosine triphosphate (ATP) to regulate critical cellular processes such as chromosome movement and microtubule dynamics. KIF18A plays a vital role in controlling microtubule length, which is crucial for maintaining proper cell function and division. Notably, increased expression levels of KIF18A have been observed in various types of cancer, indicating its potential involvement in tumour progression. Although preclinical studies have demonstrated that KIF18A is not essential for normal somatic cell division, it appears to be crucial for the survival and division of cancer cells, particularly those exhibiting chromosomal instability. This dependency makes KIF18A a promising target for developing new therapeutic strategies aimed at treating chromosomally unstable cancers. This review delves into the structural and functional aspects of KIF18A, and its role in cancer development, and evaluates current and emerging approaches to targeting KIF18A with innovative cancer treatments.

While the prevalence of cancer-associated thrombosis (CAT) is high in cancer patients, its molecular mechanisms have not been fully elucidated. Moreover, the risks of recurrent CAT events and mortality remain high in cancer patients despite the introduction of anticoagulant/antiplatelet therapy. Here, we discuss the possibility that increased plasmin activity driven by anticoagulant/antiplatelet treatment might be the major mechanism responsible for the activation of an excess of cancer-derived transforming growth factor-beta (TGF-β) originating from cancer cells and the tumour microenvironment. Hence, high coagulation and fibrinolysis rates in cancer patients may be linked to high rates of TGF-β activation, especially the excess of TGF-β derived from cancer cells. In turn, high TGF-β activation could contribute directly to maintaining high thrombotic risk and CAT recurrence in cancer patients since TGF-β signalling increases gene expression and secretion of the fibrinolysis inhibitor plasminogen activator inhibitor 1 (PAI1). Thus, TGF-β could directly contribute to the high number of deaths among patients with cancer experiencing CAT, despite anticoagulant/antiplatelet treatment. In a longer-term perspective, increased TGF-β activation, by supporting a pro-coagulant cancer microenvironment, might also accelerate cancer progression. This review aims to discuss the published evidence that might support the scenario described above, and to put forward the hypothesis that cancer patients experiencing CAT events would largely benefit from anti-TGF-β therapy.

Centrosomes serve as microtubule-organizing organelles that function in spindle pole organization, cell cycle progression, and cilia formation. A non-canonical role of centrosomes that has gained traction in recent years is the ability to act as signal transduction centers. Centrosome amplification, which includes numerical and structural aberrations of centrosomes, is a candidate hallmark of cancer. The function of centrosomes as signaling centers in cancer cells with centrosome amplification is poorly understood. Establishing a model of how cancer cells utilize centrosomes as signaling platforms will help elucidate the role of extra centrosomes in cancer cell survival and tumorigenesis. Centrosomes act in a diverse array of cellular processes, including cell migration, cell cycle progression, and proteasomal degradation. Given that cancer cells with amplified centrosomes exhibit an increased number and larger area of these signaling platforms, extra centrosomes may be acting to promote tumor development by enhancing signaling kinetics in pathways that are essential for the formation and growth of cancer. In this review, we identify the processes centrosomes are involved in as signal transduction platforms and highlight ways in which cancer cells with centrosome amplification may be taking advantage of these mechanisms.

Natural killer (NK) cells have multifaceted roles within the complex tumor milieu. They are pivotal components of innate immunity and shape the dynamic landscape of tumor-immune cell interactions, and thus can be leveraged for use in therapeutic interventions. NK-based immunotherapies have had remarkable success in hematological malignancies, but these therapies are met with many challenges in solid tumors, including neuroblastoma (NB), a childhood tumor arising from the sympathetic nervous system. With a focus on NB, this review outlines the mechanisms employed by NK cells to recognize and eliminate malignant cells, delving into the dynamic relationship between ligand-receptor interactions, cytokines, and other molecules that facilitate the cross talk between NK and NB cells. We discuss the immunomodulatory functions of NK cells and the mechanisms that contribute to loss of this immunosurveillance in NB, with a focus on how this dynamic has been utilized in recent immunotherapy advancements for NB.