Cancer and Metastasis Reviews最新文献

Extracellular vesicles (EVs) are small lipid bilayer-enclosed vesicles that mediate vital cellular communication by transferring cargo between cells. Among these, tissue-derived extracellular vesicles (Ti-EVs) stand out due to their origin from the tissue microenvironment, providing a more accurate reflection of changes in this setting. This unique advantage makes Ti-EVs valuable in investigating the intricate relationship between extracellular vesicles and cancer progression. Despite considerable research efforts exploring the association between Ti-EVs and cancers, a comprehensive clustering or grouping of these studies remains lacking. In this review, we aim to fill this gap by presenting a comprehensive synthesis of the mechanisms underlying Ti-EV generation, release, and transport within cancer tissues. Moreover, we delve into the pivotal roles that Ti-EVs play in cancer progression, shedding light on their potential as diagnostic and therapeutic tools. The review culminates in the construction of a comprehensive functional spectrum of Ti-EVs, providing a valuable reference for future research endeavors. By summarizing the current state of knowledge on Ti-EVs and their significance in tumor biology, this work contributes to a deeper understanding of cancer microenvironment dynamics and opens up avenues for harnessing Ti-EVs in diagnostic and therapeutic applications.

Modulation of histone methylation status is regarded as an important mechanism of epigenetic regulation and has substantial clinical potential for the therapy of diseases, including cancer and other disorders. The present study aimed to provide a comprehensive introduction to the enzymology of histone demethylases, as well as their cancerous roles, molecular mechanisms, therapeutic possibilities, and challenges for targeting them, in order to advance drug design for clinical therapy and highlight new insight into the mechanisms of these enzymes in cancer. A series of clinical trials have been performed to explore potential roles of histone demethylases in several cancer types. Numerous targeted inhibitors associated with immunotherapy, chemotherapy, radiotherapy, and targeted therapy have been used to exert anticancer functions. Future studies should evaluate the dynamic transformation of histone demethylases leading to carcinogenesis and explore individual therapy.

Tumor microenvironment (TME) has been demonstrated to play a significant role in tumor initiation, progression, and metastasis. Cancer-associated fibroblasts (CAFs) are the major component of TME and exhibit heterogeneous properties in their communication with tumor cells. This heterogeneity of CAFs can be attributed to various origins, including quiescent fibroblasts, mesenchymal stem cells (MSCs), adipocytes, pericytes, endothelial cells, and mesothelial cells. Moreover, single-cell RNA sequencing has identified diverse phenotypes of CAFs, with myofibroblastic CAFs (myCAFs) and inflammatory CAFs (iCAFs) being the most acknowledged, alongside newly discovered subtypes like antigen-presenting CAFs (apCAFs). Due to these heterogeneities, CAFs exert multiple functions in tumorigenesis, cancer stemness, angiogenesis, immunosuppression, metabolism, and metastasis. As a result, targeted therapies aimed at the TME, particularly focusing on CAFs, are rapidly developing, fueling the promising future of advanced tumor-targeted therapy.

The current CAR-T cell therapy products have been hampered in their druggability due to the personalized preparation required, unclear pharmacokinetic characteristics, and unpredictable adverse reactions. Enabling standardized manufacturing and having clear efficacy and pharmacokinetic characteristics are prerequisites for ensuring the effective practicality of CAR-T cell therapy drugs. This review provides a broad overview of the different approaches for controlling behaviors of CAR-T cells in vivo. The utilization of genetically modified vectors enables in vivo production of CAR-T cells, thereby abbreviating or skipping the lengthy in vitro expansion process. By equipping CAR-T cells with intricately designed control elements, using molecule switches or small-molecule inhibitors, the control of CAR-T cell activity can be achieved. Moreover, the on–off control of CAR-T cell activity would yield potential gains in phenotypic remodeling. These methods provide beneficial references for the future development of safe, controllable, convenient, and suitable for standardized production of CAR-T cell therapy products.

We identified a progenitor cell population highly enriched in samples from invasive and chemo-resistant carcinomas, characterized by a well-defined multigene signature including APOD, DCN, and LUM. This cell population has previously been labeled as consisting of inflammatory cancer-associated fibroblasts (iCAFs). The same signature characterizes naturally occurring fibro-adipogenic progenitors (FAPs) as well as stromal cells abundant in normal adipose tissue. Our analysis of human gene expression databases provides evidence that adipose stromal cells (ASCs) are recruited by tumors and undergo differentiation into CAFs during cancer progression to invasive and chemotherapy-resistant stages.

This comprehensive review explores vimentin as a pivotal therapeutic target in cancer treatment, with a primary focus on mitigating metastasis and overcoming drug resistance. Vimentin, a key player in cancer progression, is intricately involved in processes such as epithelial-to-mesenchymal transition (EMT) and resistance mechanisms to standard cancer therapies. The review delves into diverse vimentin inhibition strategies. Precision tools, including antibodies and nanobodies, selectively neutralize vimentin's pro-tumorigenic effects. DNA and RNA aptamers disrupt vimentin-associated signaling pathways through their adaptable binding properties. Innovative approaches, such as vimentin-targeted vaccines and microRNAs (miRNAs), harness the immune system and post-transcriptional regulation to combat vimentin-expressing cancer cells. By dissecting vimentin inhibition strategies across these categories, this review provides a comprehensive overview of anti-vimentin therapeutics in cancer treatment. It underscores the growing recognition of vimentin as a pivotal therapeutic target in cancer and presents a diverse array of inhibitors, including antibodies, nanobodies, DNA and RNA aptamers, vaccines, and miRNAs. These multifaceted approaches hold substantial promise for tackling metastasis and overcoming drug resistance, collectively presenting new avenues for enhanced cancer therapy.

Recent therapeutic advances have significantly uplifted the quality of life in breast cancer patients, yet several impediments block the road to disease-free survival. This involves unresponsiveness towards administered therapy, epithelial to mesenchymal transition, and metastatic progression with the eventual appearance of recurrent disease. Attainment of such characteristics is a huge adaptive challenge to which tumour cells respond by acquiring diverse phenotypically plastic states. Several signalling networks and mediators are involved in such a process. Glucocorticoid receptor being a mediator of stress response imparts prognostic significance in the context of breast carcinoma. Involvement of the glucocorticoid receptor in the signalling cascade of breast cancer phenotypic plasticity needs further elucidation. This review attempted to shed light on the inter-regulatory interactions of the glucocorticoid receptor with the mediators of the plasticity program in breast cancer; which may provide a hint for strategizing therapeutics against the glucocorticoid/glucocorticoid receptor axis so as to modulate phenotypic plasticity in breast carcinoma.

Intra-tumoural heterogeneity and cancer cell plasticity in colorectal cancer (CRC) have been key challenges to effective treatment for patients. It has been suggested that a subpopulation of LGR5-expressing cancer stem cells (CSCs) is responsible for driving tumour relapse and therapy resistance in CRC. However, studies have revealed that the LGR5^+ve CSC population is highly sensitive to chemotherapy. It has been hypothesised that another subset of tumour cells can phenotypically revert to a stem-like state in response to chemotherapy treatment which replenishes the LGR5^+ve CSC population and maintains tumour growth. Recently, a unique stem cell population marked by enriched clusterin (CLU) expression and termed the revival stem cell (RevSC) was identified in the regenerating murine intestine. This CLU-expressing cell population is quiescent during homeostasis but has the ability to survive and regenerate other stem cells upon injury. More recently, the CLU^+ve signature has been implicated in several adverse outcomes in CRC, including chemotherapy resistance and poor patient survival; however, the mechanism behind this remains undetermined. In this review, we discuss recent insights on CLU in CRC and its roles in enhancing the plasticity of cells and further consider the implications of CLU as a prospective target for therapeutic intervention.

Cancer is a complex disease displaying a variety of cell states and phenotypes. This diversity, known as cancer cell plasticity, confers cancer cells the ability to change in response to their environment, leading to increased tumor diversity and drug resistance. This review explores the intricate landscape of cancer cell plasticity, offering a deep dive into the cellular, molecular, and genetic mechanisms that underlie this phenomenon. Cancer cell plasticity is intertwined with processes such as epithelial-mesenchymal transition and the acquisition of stem cell-like features. These processes are pivotal in the development and progression of tumors, contributing to the multifaceted nature of cancer and the challenges associated with its treatment. Despite significant advancements in targeted therapies, cancer cell adaptability and subsequent therapy-induced resistance remain persistent obstacles in achieving consistent, successful cancer treatment outcomes. Our review delves into the array of mechanisms cancer cells exploit to maintain plasticity, including epigenetic modifications, alterations in signaling pathways, and environmental interactions. We discuss strategies to counteract cancer cell plasticity, such as targeting specific cellular pathways and employing combination therapies. These strategies promise to enhance the efficacy of cancer treatments and mitigate therapy resistance. In conclusion, this review offers a holistic, detailed exploration of cancer cell plasticity, aiming to bolster the understanding and approach toward tackling the challenges posed by tumor heterogeneity and drug resistance. As articulated in this review, the delineation of cellular, molecular, and genetic mechanisms underlying tumor heterogeneity and drug resistance seeks to contribute substantially to the progress in cancer therapeutics and the advancement of precision medicine, ultimately enhancing the prospects for effective cancer treatment and patient outcomes.

Cellular plasticity and therapy resistance are critical features of pancreatic cancer, a highly aggressive and fatal disease. The pancreas, a vital organ that produces digestive enzymes and hormones, is often affected by two main types of cancer: the pre-dominant ductal adenocarcinoma and the less common neuroendocrine tumors. These cancers are difficult to treat due to their complex biology characterized by cellular plasticity leading to therapy resistance. Cellular plasticity refers to the capability of cancer cells to change and adapt to different microenvironments within the body which includes acinar-ductal metaplasia, epithelial to mesenchymal/epigenetic/metabolic plasticity, as well as stemness. This plasticity allows heterogeneity of cancer cells, metastasis, and evasion of host's immune system and develops resistance to radiation, chemotherapy, and targeted therapy. To overcome this resistance, extensive research is ongoing exploring the intrinsic and extrinsic factors through cellular reprogramming, chemosensitization, targeting metabolic, key survival pathways, etc. In this review, we discussed the mechanisms of cellular plasticity involving cellular adaptation and tumor microenvironment and provided a comprehensive understanding of its role in therapy resistance and ways to overcome it.