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Nature Reviews. Disease Primers Oct 2020
Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Neoplasms
PubMed: 33060570
DOI: 10.1038/s41572-020-00226-1 -
Trends in Cancer Aug 2020Tumor metastases, that is, the development of secondary tumors in organs distant from the primary tumor, and their treatment remain a serious problem in cancer therapy.... (Review)
Review
Tumor metastases, that is, the development of secondary tumors in organs distant from the primary tumor, and their treatment remain a serious problem in cancer therapy. The unique challenges for tracking and treating tumor metastases lie in the small size, high heterogeneity, and wide dispersion to distant organs of metastases. Recently, nanomedicines, with the capacity to precisely deliver therapeutic agents to both primary and secondary tumors, have demonstrated many potential benefits for metastatic cancer theranostics. Given the remarkable progression in emerging nanotherapeutics for antimetastatic treatment, it is timely to summarize the latest advances in this field. This review highlights the rationale, advantages, and challenges for integrating biomedical nanotechnology with cancer biology to develop antimetastatic nanotherapeutics.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Molecular Imaging; Molecular Probes; Nanoparticles; Neoplasm Metastasis; Neoplastic Cells, Circulating; Theranostic Nanomedicine; Tumor Microenvironment
PubMed: 32448754
DOI: 10.1016/j.trecan.2020.05.001 -
American Journal of Physiology. Cell... May 2023Cancer-associated metastasis is the primary cause of morbidity and mortality. Yet, its underlying biological mechanism remains poorly understood. Efforts to prevent or... (Review)
Review
Cancer-associated metastasis is the primary cause of morbidity and mortality. Yet, its underlying biological mechanism remains poorly understood. Efforts to prevent or delay metastasis require a deep understanding of the underlying molecular mechanisms. However, continued advancement in cancer biology research has improved the comprehensive understanding of some of the molecular keystones of the dissemination process. However, the emergence of new paradigms in the study of metastasis intuitively recognizes the involvement of genetics, epigenetics, extrinsic traits, and tumor microenvironment in metastatic initiation, progression, and colonization. On their way to the target site, the disseminated tumor cells interact with multiplex of proteins and cells. Identification of mechanisms underlying metastatic program is crucial for developing effective and efficient therapeutic interventions. In this review, we discuss details about recent advancements in the field of metastasis and organotropism, also highlights the role of genetics, epigenetics, exosomes, circadian rhythm, microbiome, integrins, and other adhesion molecules, and chemokines in the regulation of metastatic events.
Topics: Humans; Integrins; Exosomes; Neoplasms; Neoplasm Metastasis; Epithelial-Mesenchymal Transition; Tumor Microenvironment
PubMed: 36939199
DOI: 10.1152/ajpcell.00348.2022 -
British Journal of Cancer Jan 2021Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract... (Review)
Review
Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, that keep anti-tumour T cells active. However, not every patient with metastatic disease benefits from this class of drugs and patients often develop resistance to these therapies over time. Tremendous research effort is now underway to uncover new immunotherapeutic targets that can be used in patients who are refractory to anti-CTLA-4 or anti-PD-1 treatment. Here, we discuss results from experimental model systems demonstrating that modulating the immune response can negatively affect metastasis formation. We focus on molecules that boost anti-tumour immune cells and opportunities to block immunosuppression, as well as cell-based therapies with enhanced tumour recognition properties for solid tumours. We also present a list of challenges in treating metastatic disease with immunotherapy that must be considered in order to move laboratory observations into clinical practice and maximise patient benefit.
Topics: Animals; Humans; Immunotherapy; Neoplasm Metastasis; Neoplasms
PubMed: 33262520
DOI: 10.1038/s41416-020-01160-5 -
Growth Factors (Chur, Switzerland) Aug 2022Organ-specific metastasis to secondary organs is dependent on the formation of a supportive pre-metastatic niche. This tissue-specific microenvironmental response is... (Review)
Review
Organ-specific metastasis to secondary organs is dependent on the formation of a supportive pre-metastatic niche. This tissue-specific microenvironmental response is thought to be mediated by mutational and epigenetic changes to primary tumour cells resulting in altered cross-talk between cell types. This response is augmented through the release of tumour and stromal signalling mediators including cytokines, chemokines, exosomes and growth factors. Although researchers have elucidated some of the cancer-promoting features that are bespoke to organotropic metastasis to the lungs, it remains unclear if these are organ-specific or generic between organs. Understanding the mechanisms that mediate the metastasis-promoting synergy between the host microenvironment, immunity, and pulmonary structures may elucidate predictive, prognostic and therapeutic markers that could be targeted to reduce the metastatic burden of disease. Herein, we give an updated summary of the known cellular and molecular mechanisms that contribute to the formation of the lung pre-metastatic niche and tissue-specific metastasis.
Topics: Exosomes; Humans; Lung; Neoplasm Metastasis; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 35861197
DOI: 10.1080/08977194.2022.2087520 -
Expert Review of Anticancer Therapy Feb 2020: Metastatic cancers are extremely difficult to treat, and account for the vast majority of cancer-related deaths. The dissemination of tumor cells to distant sites is... (Review)
Review
: Metastatic cancers are extremely difficult to treat, and account for the vast majority of cancer-related deaths. The dissemination of tumor cells to distant sites is highly dynamic, asynchronous, and involves both tumor and host intrinsic factors. Effective therapeutic targets to block metastasis will need to disrupt key pathways that are required for multiple stages of metastasis.: This review discusses the heterogeneity of cancers and metastasis, with an emphasis on motility as a key driver trait of metastasis. Recent metastatic cancer studies that identified either host or cancer cell intrinsic factors important for metastasis, using single gene-deficient animal models or 3D intravital imaging of avian embryo models, are also discussed. Potential metastatic blocking targets are listed as they relate to metastatic cancer therapy.: The development of metastatic disease is a complex interplay of genetic and epigenetic factors from the host and cancer cells acting in a patient-specific manner. Inhibiting key driver traits of metastasis should yield survival benefit at any stage of the disease, and we look forward to the next generation of personalized medicines for cancer therapy that target cancer cell motility for increased therapeutic efficacy.
Topics: Animals; Cell Movement; Epigenesis, Genetic; Humans; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasms; Precision Medicine
PubMed: 31997674
DOI: 10.1080/14737140.2020.1718496 -
Clinical & Experimental Metastasis Aug 2021The metastatic process is arduous. Cancer cells must escape the confines of the primary tumor, make their way into and travel through the circulation, then survive and... (Review)
Review
The metastatic process is arduous. Cancer cells must escape the confines of the primary tumor, make their way into and travel through the circulation, then survive and proliferate in unfavorable microenvironments. A key question is how cancer cells overcome these multiple barriers to orchestrate distant organ colonization. Accumulating evidence in human patients and animal models supports the hypothesis that clusters of tumor cells can complete the entire metastatic journey in a process referred to as collective metastasis. Here we highlight recent studies unraveling how multicellular coordination, via both physical and biochemical coupling of cells, induces cooperative properties advantageous for the completion of metastasis. We discuss conceptual challenges and unique mechanisms arising from collective dissemination that are distinct from single cell-based metastasis. Finally, we consider how the dissection of molecular transitions regulating collective metastasis could offer potential insight into cancer therapy.
Topics: Cell Communication; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating; Tumor Microenvironment
PubMed: 34254215
DOI: 10.1007/s10585-021-10111-0 -
International Journal of Radiation... Nov 2020In this review, we discuss the oligometastatic state, with a focus on its current and future relevance within the field of radiation therapy. We first outline the scope... (Review)
Review
In this review, we discuss the oligometastatic state, with a focus on its current and future relevance within the field of radiation therapy. We first outline the scope of the problem and the evolving understanding of metastatic disease existing along a spectrum. We then transition to a discussion of the clinical data that led to the formulation of the oligometastatic hypothesis, delving in some detail into the clinical factors associated with improved outcomes in the setting of local therapy-whether surgical or radiotherapeutic. In particular, we highlight the marked limitations of using clinical criteria alone to determine the absence or presence of true extracranial oligometastatic disease. After this, we briefly discuss the radiation therapy literature that has recently demonstrated benefits in cancer-specific outcomes with ablative treatment of oligometastatic disease. We emphasize data in the setting of non-small cell lung cancer and prostate cancer and briefly discuss the importance of our enhanced ability to detect occult metastatic disease with improved imaging technologies. After noting that resulted and ongoing prospective trials of ablative radiation therapy use the most rudimentary of oligometastatic classifiers-number of metastases-as their inclusion criteria, we transition to our core argument: a growing body of preclinical and translational work aims to refine the definition of oligometastatic disease using molecular features. We address genomic, epigenetic, and immunologic features that have, across histology, demonstrated an improved ability to prognosticate when combined with classic clinical correlates of oligometastatic disease. We also discuss studies that suggest particular molecular targets which, when manipulated for therapeutic purposes, have the potential to revert the polymetastatic phenotype to the oligometastatic one. We conclude with what we believe are the repercussions of this work for radiation therapy trials and clinical practice, and the importance of enriching and supporting these inquiries for the future of our field.
Topics: Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Colorectal Neoplasms; Epigenesis, Genetic; Humans; Liver Neoplasms; Lung Neoplasms; Male; Metastasectomy; Molecular Targeted Therapy; Neoplasm Metastasis; Prostatic Neoplasms
PubMed: 32976785
DOI: 10.1016/j.ijrobp.2020.02.019 -
Nature Oct 2022Cancer progression is driven in part by genomic alterations. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations,... (Randomized Controlled Trial)
Randomized Controlled Trial
Cancer progression is driven in part by genomic alterations. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations, leading to the concept that generation of genomic profiling in patients with cancer could allow the selection of effective therapies. Although DNA sequencing has been implemented in practice, it remains unclear how to use its results. A total of 1,462 patients with HER2-non-overexpressing metastatic breast cancer were enroled to receive genomic profiling in the SAFIR02-BREAST trial. Two hundred and thirty-eight of these patients were randomized in two trials (nos. NCT02299999 and NCT03386162) comparing the efficacy of maintenance treatment with a targeted therapy matched to genomic alteration. Targeted therapies matched to genomics improves progression-free survival when genomic alterations are classified as level I/II according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted hazards ratio (HR): 0.41, 90% confidence interval (CI): 0.27-0.61, P < 0.001), but not when alterations are unselected using ESCAT (adjusted HR: 0.77, 95% CI: 0.56-1.06, P = 0.109). No improvement in progression-free survival was observed in the targeted therapies arm (unadjusted HR: 1.15, 95% CI: 0.76-1.75) for patients presenting with ESCAT alteration beyond level I/II. Patients with germline BRCA1/2 mutations (n = 49) derived high benefit from olaparib (gBRCA1: HR = 0.36, 90% CI: 0.14-0.89; gBRCA2: HR = 0.37, 90% CI: 0.17-0.78). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with metastatic breast cancer.
Topics: Breast Neoplasms; Clinical Decision-Making; DNA Mutational Analysis; Disease Progression; Female; Genes, BRCA1; Genes, BRCA2; Genome, Human; Genomics; Humans; Neoplasm Metastasis; Phthalazines; Piperazines
PubMed: 36071165
DOI: 10.1038/s41586-022-05068-3 -
Wiley Interdisciplinary Reviews.... Jul 2021Cancer metastasis, the spread of disease from a primary to a distal site through the circulatory or lymphatic systems, accounts for over 90% of all cancer related... (Review)
Review
Cancer metastasis, the spread of disease from a primary to a distal site through the circulatory or lymphatic systems, accounts for over 90% of all cancer related deaths. Despite significant progress in the field of cancer therapy in recent years, mortality rates remain dramatically higher for patients with metastatic disease versus those with local or regional disease. Although there is clearly an urgent need to develop drugs that inhibit cancer spread, the overwhelming majority of anticancer therapies that have been developed to date are designed to inhibit tumor growth but fail to address the key stages of the metastatic process: invasion, intravasation, circulation, extravasation, and colonization. There is growing interest in engineering targeted therapeutics, such as antibody drugs, that inhibit various steps in the metastatic cascade. We present an overview of antibody therapeutic approaches, both in the pipeline and in the clinic, that disrupt the essential mechanisms that underlie cancer metastasis. These therapies include classes of antibodies that indirectly target metastasis, including anti-integrin, anticadherin, and immune checkpoint blocking antibodies, as well as monoclonal and bispecific antibodies that are specifically designed to interrupt disease dissemination. Although few antimetastatic antibodies have achieved clinical success to date, there are many promising candidates in various stages of development, and novel targets and approaches are constantly emerging. Collectively, these efforts will enrich our understanding of the molecular drivers of metastasis, and the new strategies that arise promise to have a profound impact on the future of cancer therapeutic development. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
Topics: Antibodies; Drug Delivery Systems; Humans; Immunotherapy; Nanomedicine; Neoplasm Metastasis; Neoplasms
PubMed: 33463090
DOI: 10.1002/wnan.1698