Amanda Mendes da Silva, Veronika Yevdokimova, Yannick D Benoit
{"title":"Sam68 is a druggable vulnerability point in cancer stem cells.","authors":"Amanda Mendes da Silva, Veronika Yevdokimova, Yannick D Benoit","doi":"10.1007/s10555-023-10145-8","DOIUrl":"10.1007/s10555-023-10145-8","url":null,"abstract":"<p><p>Sam68 (Src associated in mitosis of 68 kDa) is an RNA-binding and multifunctional protein extensively characterized in numerous cellular functions, such as RNA processing, cell cycle regulation, kinase- and growth factor signaling. Recent investigations highlighted Sam68 as a primary target of a class of reverse-turn peptidomimetic drugs, initially developed as inhibitors of Wnt/β-catenin mediated transcription. Further investigations on such compounds revealed their capacity to selectively eliminate cancer stem cell (CSC) activity upon engaging Sam68. This work highlighted previously unappreciated roles for Sam68 in the maintenance of neoplastic self-renewal and tumor-initiating functions. Here, we discuss the implication of Sam68 in tumorigenesis, where central findings support its contribution to chromatin regulation processes essential to CSCs. We also review advances in CSC-targeting drug discovery aiming to modulate Sam68 cellular distribution and protein-protein interactions. Ultimately, Sam68 constitutes a vulnerability point of CSCs and an attractive therapeutic target to impede neoplastic stemness in human tumors.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":" ","pages":"441-456"},"PeriodicalIF":9.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bandari BharathwajChetty, Anjana Sajeev, Ravichandran Vishwa, Babu Santha Aswani, Mohammed S Alqahtani, Mohamed Abbas, Ajaikumar B Kunnumakkara
{"title":"Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.","authors":"Bandari BharathwajChetty, Anjana Sajeev, Ravichandran Vishwa, Babu Santha Aswani, Mohammed S Alqahtani, Mohamed Abbas, Ajaikumar B Kunnumakkara","doi":"10.1007/s10555-024-10171-0","DOIUrl":"10.1007/s10555-024-10171-0","url":null,"abstract":"<p><p>Recent advances have brought forth the complex interplay between tumor cell plasticity and its consequential impact on drug resistance and tumor recurrence, both of which are critical determinants of neoplastic progression and therapeutic efficacy. Various forms of tumor cell plasticity, instrumental in facilitating neoplastic cells to develop drug resistance, include epithelial-mesenchymal transition (EMT) alternatively termed epithelial-mesenchymal plasticity, the acquisition of cancer stem cell (CSC) attributes, and transdifferentiation into diverse cell lineages. Nuclear receptors (NRs) are a superfamily of transcription factors (TFs) that play an essential role in regulating a multitude of cellular processes, including cell proliferation, differentiation, and apoptosis. NRs have been implicated to play a critical role in modulating gene expression associated with tumor cell plasticity and drug resistance. This review aims to provide a comprehensive overview of the current understanding of how NRs regulate these key aspects of cancer biology. We discuss the diverse mechanisms through which NRs influence tumor cell plasticity, including EMT, stemness, and metastasis. Further, we explore the intricate relationship between NRs and drug resistance, highlighting the impact of NR signaling on chemotherapy, radiotherapy and targeted therapies. We also discuss the emerging therapeutic strategies targeting NRs to overcome tumor cell plasticity and drug resistance. This review also provides valuable insights into the current clinical trials that involve agonists or antagonists of NRs modulating various aspects of tumor cell plasticity, thereby delineating the potential of NRs as therapeutic targets for improved cancer treatment outcomes.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":" ","pages":"321-362"},"PeriodicalIF":9.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ravichandran Vishwa, Bandari BharathwajChetty, Sosmitha Girisa, Babu Santha Aswani, Mohammed S Alqahtani, Mohamed Abbas, Mangala Hegde, Ajaikumar B Kunnumakkara
{"title":"Lipid metabolism and its implications in tumor cell plasticity and drug resistance: what we learned thus far?","authors":"Ravichandran Vishwa, Bandari BharathwajChetty, Sosmitha Girisa, Babu Santha Aswani, Mohammed S Alqahtani, Mohamed Abbas, Mangala Hegde, Ajaikumar B Kunnumakkara","doi":"10.1007/s10555-024-10170-1","DOIUrl":"10.1007/s10555-024-10170-1","url":null,"abstract":"<p><p>Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt to their specific energy needs. The Warburg effect benefits cancer cells in both hypoxic and normoxic conditions and is a well-studied reprogramming of metabolism in cancer. Interestingly, the alteration of other metabolic pathways, especially lipid metabolism has also grabbed the attention of scientists worldwide. Lipids, primarily consisting of fatty acids, phospholipids and cholesterol, play essential roles as structural component of cell membrane, signalling molecule and energy reserves. This reprogramming primarily involves aberrations in the uptake, synthesis and breakdown of lipids, thereby contributing to the survival, proliferation, invasion, migration and metastasis of cancer cells. The development of resistance to the existing treatment modalities poses a major challenge in the field of cancer therapy. Also, the plasticity of tumor cells was reported to be a contributing factor for the development of resistance. A number of studies implicated that dysregulated lipid metabolism contributes to tumor cell plasticity and associated drug resistance. Therefore, it is important to understand the intricate reprogramming of lipid metabolism in cancer cells. In this review, we mainly focused on the implication of disturbed lipid metabolic events on inducing tumor cell plasticity-mediated drug resistance. In addition, we also discussed the concept of lipid peroxidation and its crucial role in phenotypic switching and resistance to ferroptosis in cancer cells. Elucidating the relationship between lipid metabolism, tumor cell plasticity and emergence of resistance will open new opportunities to develop innovative strategies and combinatorial approaches for the treatment of cancer.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":" ","pages":"293-319"},"PeriodicalIF":9.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epigenetic reprogramming of T cells: unlocking new avenues for cancer immunotherapy.","authors":"Vipin Singh, Sandhik Nandi, Aritra Ghosh, Santanu Adhikary, Shravanti Mukherjee, Siddhartha Roy, Chandrima Das","doi":"10.1007/s10555-024-10167-w","DOIUrl":"10.1007/s10555-024-10167-w","url":null,"abstract":"<p><p>T cells, a key component of cancer immunotherapy, undergo a variety of histone modifications and DNA methylation changes since their bone marrow progenitor stages before developing into CD8<sup>+</sup> and CD4<sup>+</sup> T cells. These T cell types can be categorized into distinct subtypes based on their functionality and properties, such as cytotoxic T cells (Tc), helper T cells (Th), and regulatory T cells (Treg) as subtypes for CD8<sup>+</sup> and CD4<sup>+</sup> T cells. Among these, the CD4<sup>+</sup> CD25<sup>+</sup> Tregs potentially contribute to cancer development and progression by lowering T effector (Teff) cell activity under the influence of the tumor microenvironment (TME). This contributes to the development of therapeutic resistance in patients with cancer. Subsequently, these individuals become resistant to monoclonal antibody therapy as well as clinically established immunotherapies. In this review, we delineate the different epigenetic mechanisms in cancer immune response and its involvement in therapeutic resistance. Furthermore, the possibility of epi-immunotherapeutic methods based on histone deacetylase inhibitors and histone methyltransferase inhibitors are under investigation. In this review we highlight EZH2 as the principal driver of cancer cell immunoediting and an immune escape regulator. We have addressed in detail how understanding T cell epigenetic regulation might bring unique inventive strategies to overcome drug resistance and increase the efficacy of cancer immunotherapy.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":" ","pages":"175-195"},"PeriodicalIF":9.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation.","authors":"Milad Ashrafizadeh, Wei Zhang, Yu Tian, Gautam Sethi, Xianbin Zhang, Aiming Qiu","doi":"10.1007/s10555-024-10168-9","DOIUrl":"10.1007/s10555-024-10168-9","url":null,"abstract":"<p><p>Prostate cancer (PCa) is a malignant disorder of prostate gland being asymptomatic in early stages and high metastatic potential in advanced stages. The chemotherapy and surgical resection have provided favourable prognosis of PCa patients, but advanced and aggressive forms of PCa including CRPC and AVPC lack response to therapy properly, and therefore, prognosis of patients is deteriorated. At the advanced stages, PCa cells do not respond to chemotherapy and radiotherapy in a satisfactory level, and therefore, therapy resistance is emerged. Molecular profile analysis of PCa cells reveals the apoptosis suppression, pro-survival autophagy induction, and EMT induction as factors in escalating malignant of cancer cells and development of therapy resistance. The dysregulation in molecular profile of PCa including upregulation of STAT3 and PI3K/Akt, downregulation of STAT3, and aberrant expression of non-coding RNAs are determining factor for response of cancer cells to chemotherapy. Because of prevalence of drug resistance in PCa, combination therapy including co-utilization of anti-cancer drugs and nanotherapeutic approaches has been suggested in PCa therapy. As a result of increase in DNA damage repair, PCa cells induce radioresistance and RelB overexpression prevents irradiation-mediated cell death. Similar to chemotherapy, nanomaterials are promising for promoting radiosensitivity through delivery of cargo, improving accumulation in PCa cells, and targeting survival-related pathways. In respect to emergence of immunotherapy as a new tool in PCa suppression, tumour cells are able to increase PD-L1 expression and inactivate NK cells in mediating immune evasion. The bioinformatics analysis for evaluation of drug resistance-related genes has been performed.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":" ","pages":"229-260"},"PeriodicalIF":9.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sajad Fakhri, Seyed Zachariah Moradi, Fatemeh Abbaszadeh, Farahnaz Faraji, Roshanak Amirian, Dona Sinha, Emily G McMahon, Anupam Bishayee
{"title":"Targeting the key players of phenotypic plasticity in cancer cells by phytochemicals.","authors":"Sajad Fakhri, Seyed Zachariah Moradi, Fatemeh Abbaszadeh, Farahnaz Faraji, Roshanak Amirian, Dona Sinha, Emily G McMahon, Anupam Bishayee","doi":"10.1007/s10555-023-10161-8","DOIUrl":"10.1007/s10555-023-10161-8","url":null,"abstract":"<p><p>Plasticity of phenotypic traits refers to an organism's ability to change in response to environmental stimuli. As a result, the response may alter an organism's physiological state, morphology, behavior, and phenotype. Phenotypic plasticity in cancer cells describes the considerable ability of cancer cells to transform phenotypes through non-genetic molecular signaling activities that promote therapy evasion and tumor metastasis via amplifying cancer heterogeneity. As a result of metastable phenotypic state transitions, cancer cells can tolerate chemotherapy or develop transient adaptive resistance. Therefore, new findings have paved the road in identifying factors and agents that inhibit or suppress phenotypic plasticity. It has also investigated novel multitargeted agents that may promise new effective strategies in cancer treatment. Despite the efficiency of conventional chemotherapeutic agents, drug toxicity, development of resistance, and high-cost limit their use in cancer therapy. Recent research has shown that small molecules derived from natural sources are capable of suppressing cancer by focusing on the plasticity of phenotypic responses. This systematic, comprehensive, and critical review analyzes the current state of knowledge regarding the ability of phytocompounds to target phenotypic plasticity at both preclinical and clinical levels. Current challenges/pitfalls, limitations, and future perspectives are also discussed.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":" ","pages":"261-292"},"PeriodicalIF":9.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sabrean Farhan Jawad, Farag M A Altalbawy, Radhwan M Hussein, Ali Abdulhussain Fadhil, Mohammed Abed Jawad, Rahman S Zabibah, Tasneem Younus Taraki, Chakrabhavi Dhananjaya Mohan, Kanchugarakoppal S Rangappa
{"title":"The strict regulation of HIF-1α by non-coding RNAs: new insight towards proliferation, metastasis, and therapeutic resistance strategies.","authors":"Sabrean Farhan Jawad, Farag M A Altalbawy, Radhwan M Hussein, Ali Abdulhussain Fadhil, Mohammed Abed Jawad, Rahman S Zabibah, Tasneem Younus Taraki, Chakrabhavi Dhananjaya Mohan, Kanchugarakoppal S Rangappa","doi":"10.1007/s10555-023-10129-8","DOIUrl":"10.1007/s10555-023-10129-8","url":null,"abstract":"<p><p>The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":" ","pages":"5-27"},"PeriodicalIF":9.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9952167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aranka Brockmueller, Anjana Sajeev, Lenka Koklesova, Samson Mathews Samuel, Peter Kubatka, Dietrich Büsselberg, Ajaikumar B Kunnumakkara, Mehdi Shakibaei
{"title":"Resveratrol as sensitizer in colorectal cancer plasticity.","authors":"Aranka Brockmueller, Anjana Sajeev, Lenka Koklesova, Samson Mathews Samuel, Peter Kubatka, Dietrich Büsselberg, Ajaikumar B Kunnumakkara, Mehdi Shakibaei","doi":"10.1007/s10555-023-10126-x","DOIUrl":"10.1007/s10555-023-10126-x","url":null,"abstract":"<p><p>Despite tremendous medical treatment successes, colorectal cancer (CRC) remains a leading cause of cancer deaths worldwide. Chemotherapy as monotherapy can lead to significant side effects and chemoresistance that can be linked to several resistance-activating biological processes, including an increase in inflammation, cellular plasticity, multidrug resistance (MDR), inhibition of the sentinel gene p53, and apoptosis. As a consequence, tumor cells can escape the effectiveness of chemotherapeutic agents. This underscores the need for cross-target therapeutic approaches that are not only pharmacologically safe but also modulate multiple potent signaling pathways and sensitize cancer cells to overcome resistance to standard drugs. In recent years, scientists have been searching for natural compounds that can be used as chemosensitizers in addition to conventional medications for the synergistic treatment of CRC. Resveratrol, a natural polyphenolic phytoalexin found in various fruits and vegetables such as peanuts, berries, and red grapes, is one of the most effective natural chemopreventive agents. Abundant in vitro and in vivo studies have shown that resveratrol, in interaction with standard drugs, is an effective chemosensitizer for CRC cells to chemotherapeutic agents and thus prevents drug resistance by modulating multiple pathways, including transcription factors, epithelial-to-mesenchymal transition-plasticity, proliferation, metastasis, angiogenesis, cell cycle, and apoptosis. The ability of resveratrol to modify multiple subcellular pathways that may suppress cancer cell plasticity and reversal of chemoresistance are critical parameters for understanding its anti-cancer effects. In this review, we focus on the chemosensitizing properties of resveratrol in CRC and, thus, its potential importance as an additive to ongoing treatments.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":" ","pages":"55-85"},"PeriodicalIF":9.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10264333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Colorectal cancer: a comprehensive review of carcinogenesis, diagnosis, and novel strategies for classified treatments","authors":"Roya Abedizadeh, Fateme Majidi, Hamid Reza Khorasani, Hassan Abedi, Davood Sabour","doi":"10.1007/s10555-023-10158-3","DOIUrl":"https://doi.org/10.1007/s10555-023-10158-3","url":null,"abstract":"<p>Colorectal cancer is the third most common and the second deadliest cancer worldwide. To date, colorectal cancer becomes one of the most important challenges of the health system in many countries. Since the clinical symptoms of this cancer appear in the final stages of the disease and there is a significant golden time between the formation of polyps and the onset of cancer, early diagnosis can play a significant role in reducing mortality. Today, in addition to colonoscopy, minimally invasive methods such as liquid biopsy have received much attention. The treatment of this complex disease has been mostly based on traditional treatments including surgery, radiotherapy, and chemotherapy; the high mortality rate indicates a lack of success for current treatment methods. Moreover, disease recurrence is another problem of traditional treatments. Recently, new approaches such as targeted therapy, immunotherapy, and nanomedicine have opened new doors for cancer treatment, some of which have already entered the market, and many methods have shown promising results in clinical trials. The success of immunotherapy in the treatment of refractory disease, the introduction of these methods into neoadjuvant therapy, and the successful results in tumor shrinkage without surgery have made immunotherapy a tough competitor for conventional treatments. It seems that the combination of those methods with such targeted therapies will go through promising changes in the future of colorectal cancer treatment.</p>","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"38 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138743162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}