This systematic literature review (CRD42023393903) and a Bayesian network meta-analysis (NMA) aimed to assess the relative safety profile of first-line targeted therapies (acalabrutinib, ibrutinib, obinutuzumab, ofatumumab, pirtobrutinib, ublituximab, umbralisib, venetoclax, zanubrutinib) in chronic lymphocytic leukaemia (CLL) patients with advanced age and/or comorbidities. The NMA revealed that zanubrutinib was the safest treatment option in terms of the overall safety profile (e.g., serious adverse events [AEs] grade 1-5), followed by venetoclax-obinutuzumab, which showed an advantage in terms of AEs grade 1-5. The use of Bruton\'s tyrosine kinase inhibitor (BTKi) monotherapy was more favourable in terms of the risk of haematological AEs, but chemoimmunotherapy showed advantages in terms of cardiovascular, gastrointestinal, and infectious AEs. The risk of secondary cancers was similar between treatments. In conclusion, targeted therapies are associated with variable and clinically relevant AEs. The therapies appear to be safer when used as monotherapy rather than in combination with immunological agents in naïve CLL patients with advanced age and/or comorbidities.

Histone chaperones are integral to chromatin dynamics, facilitating the assembly and disassembly of nucleosomes, thereby playing a crucial role in regulating gene expression and maintaining genomic stability. Moreover, they prevent aberrant histone interactions prior to chromatin assembly. Disruption in histone chaperone function may result in genomic instability, which is implicated in pathogenesis. This review aims to elucidate the role of histone chaperones in cancer pathologies and explore their potential as therapeutic targets. Histone chaperones have been found to be dysregulated in various cancers, with alterations in expression levels, mutations, or aberrant interactions leading to tumorigenesis and cancer progression. In addition, this review intends to highlight the molecular mechanisms of interactions between histone chaperones and oncogenic factors, underscoring their roles in cancer cell survival and proliferation. The dysregulation of histone chaperones is significantly correlated with cancer development, establishing them as active contributors to cancer pathology and viable targets for therapeutic intervention. This review advocates for continued research into histone chaperone-targeted therapies, which hold potential for precision medicine in oncology. Future advancements in understanding chaperone functions and interactions are anticipated to lead to novel cancer treatments, enhancing patient care and outcomes.

New advancements in medicine have paved the way for targeted therapies and immune checkpoint inhibitors (ICIs), which have become mainstays of cancer therapy. Targeted therapies work by pinpointing specific molecules in cancer pathways and inhibiting their function, while ICIs target irregularities in the immune system and DNA repair, participating in the induction of cell death. Although these agents have demonstrated great efficacy in treating a diverse set of cancers, they can frequently provoke serious dermatologic adverse effects. The side effects caused by an ICI are classified as immune-related adverse events since ICIs are immunomodulating, while the cutaneous side effects of targeted therapies are known as dermatologic adverse effects. Multiple studies have reported psoriasis and psoriasiform eruptions among the side effects observed in neoplastic patients receiving targeted therapies or ICIs. Psoriasis is an immune-mediated disease characterized by overactive T-cells and keratinocytes. To conduct this review, we retrieved 1363 studies from the PubMed database published between 2008 and 2023 using the terms \"psoriasis\" AND \"cancer treatment.\" Many of these studies aimed to understand how patients with cancer receiving treatment may develop or even achieve psoriasis remission. Given that cancer and psoriasis involve a delicate balance between immune activation and suppression, ICIs and targeted therapies might produce varying effects. The aim of this review was to explore the relationship between psoriasis and cancer therapeutics while also highlighting the need to prioritize proper management of cutaneous side effects in neoplastic patients.

UNASSIGNED: Thymic carcinomas are rare tumors derived from thymic epithelial cells. Owing to their rarity, the search for molecular biology has been conducted in combination with thymoma as one histological subtype, and only a few studies have exclusively focused on thymic carcinoma. Currently, no therapy is more effective than complete surgical resection, and the development of novel therapies, including targeted therapies, is hampered. In this review, we summarize the knowledge regarding altered genes and pathways in thymic carcinoma with recent preclinical and clinical targeted therapies.
UNASSIGNED: We conducted a narrative review of the relevant English literature available in PubMed and Google Scholar on genomic characteristics and targeted therapies for thymic carcinoma.
UNASSIGNED: Although the literature consists of a relatively small series, it suggests that the frequently involved genes or pathways associated with thymic carcinoma are tumor suppressor genes, including TP53 and CDKN2A/B, and the receptor tyrosine kinase pathway. Targeted therapy demonstrated antitumor activity with encouraging results. However, potential predictive biomarkers have not been identified and the response to these therapies appears to be irrelevant to gene alterations.
UNASSIGNED: Some studies have revealed the molecular characteristics of thymic carcinoma, although the results of these studies have shown a different pattern of gene alterations. The further accumulation of data would be helpful in revealing the genomic landscape and establishing molecular-targeted therapies.

Triple-negative breast cancer (TNBC) poses significant challenges in oncology due to its aggressive nature, limited treatment options, and poorer prognosis compared to other breast cancer subtypes. This comprehensive review examines the therapeutic and diagnostic landscape of TNBC, highlighting current strategies, emerging therapies, and future directions. Targeted therapies, including PARP inhibitors, immune checkpoint inhibitors, and EGFR inhibitors, hold promise for personalized treatment approaches. Challenges in identifying novel targets, exploring combination therapies, and developing predictive biomarkers must be addressed to optimize targeted therapy in TNBC. Immunotherapy represents a transformative approach in TNBC treatment, yet challenges in biomarker identification, combination strategies, and overcoming resistance persist. Precision medicine approaches offer opportunities for tailored treatment based on tumor biology, but integration of multi-omics data and clinical implementation present challenges requiring innovative solutions. Despite these challenges, ongoing research efforts and collaborative initiatives offer hope for improving outcomes and advancing treatment strategies in TNBC. By addressing the complexities of TNBC biology and developing effective therapeutic approaches, personalized treatments can be realized, ultimately enhancing the lives of TNBC patients. Continued research, clinical trials, and interdisciplinary collaborations are essential for realizing this vision and making meaningful progress in TNBC management.

BACKGROUND: Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs\' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs\' high plasticity.
OBJECTIVE: To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms.
METHODS: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including \"glioma stem cells\", \"radiotherapy\", \"chemotherapy\", \"resistance\", and \"targeted therapies\". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR).
RESULTS: In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors (e.g., LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies (e.g., cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies.
CONCLUSIONS: GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.

Targeted therapies represent major advancements in the treatment of chronic skin conditions such as psoriasis. While previous studies have shown an increased risk of melanoma and non-melanoma skin cancer (NMSC) in patients receiving TNF-α inhibitors, the risks associated with newer biologics (IL-12/23 inhibitors, IL-23 inhibitors, IL-17 inhibitors) and Janus kinase (JAK) inhibitors remain less known. Using a systematic and meta-analytical approach, we aimed to summarize the currently available literature concerning skin cancer risk in patients treated with targeted therapies. The MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched to find studies reporting the incidence rates (IR) of melanoma and NMSC in patients with psoriasis and psoriatic arthritis treated with biologics or JAK inhibitors. Nineteen studies were included in the analysis with a total of 13,739 patients. The overall IR of melanoma was 0.08 (95% CI, 0.05-0.15) events per 100 PYs and the overall IR of NMSC was 0.45 (95% CI, 0.33-0.61) events per 100 PYs. The IRs of melanoma were comparable across patients treated with IL-17 inhibitors, IL-23 inhibitors, and JAK inhibitors, while the IRs of NMSC were higher in patients treated with JAK inhibitors than in those treated with biologics. Prospective, long-term cohort studies are required to reliably assess the risks associated with novel targeted therapies.

Cancer metastasis is the leading cause of cancer-related death. Metastasis occurs at all stages of tumor development, with unexplored changes occurring at the primary site and distant colonization sites. The growing understanding of the metastatic process of tumor cells has contributed to the emergence of better treatment options and strategies. This review summarizes a range of features related to tumor cell metastasis and nanobased drug delivery systems for inhibiting tumor metastasis. The mechanisms of tumor metastasis in the ideal order of metastatic progression were summarized. We focus on the prominent role of nanocarriers in the treatment of tumor metastasis, summarizing the latest applications of nanocarriers in combination with drugs to target important components and processes of tumor metastasis and providing ideas for more effective nanodrug delivery systems.

This comprehensive review delves into cancer\'s complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression and therapeutic strategies. This review covers cancer cell migration, invasion, and colonization of distant organs, emphasizing the significance of cell adhesion and the intricate metastasis process. Inhibition approaches targeting adhesion molecules, such as integrins and cadherins, are discussed. Overall, this review contributes significantly to advancing cancer research and developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising therapeutic targets to alleviate adhesion and metastasis of cancer cells. The effectiveness of integrin-blocking antibodies, small molecule inhibitors targeting Focal adhesion kinase (FAK) and the Transforming Growth Factor β (TGF-β) pathway, and combination therapies underscores their potential to disrupt focal adhesions and control epithelial-mesenchymal transition processes. The identification of as FAK, Src, β-catenin and SMAD4 offers valuable starting points for further research and the development of targeted therapies. The complex interrelationships between adhesion and metastatic signaling networks will be relevant to the development of new treatment approaches.

MET alterations, including MET exon 14 skipping variants, MET amplification, MET overexpression, and MET fusion, play pivotal roles in primary tumorigenesis and acquired resistance to targeted therapies, especially EGFR tyrosine kinase inhibitors. They represent important diagnostic, prognostic, and predictive biomarkers in many solid tumor types. However, the detection of MET alterations is challenging due to the complexity of MET alterations and the diversity of platform technologies. Therefore, techniques with high sensitivity, specificity, and reliable molecular detection accuracy are needed to overcome such hindrances and aid in biomarker-guided therapies. The current review emphasizes the role of MET alterations as oncogenic drivers in a variety of cancers and their involvement in the development of resistance to targeted therapies. Moreover, our review provides an overview of and recommendations on the selection of various cross-platform technologies for the detection of MET exon 14 skipping variants, MET amplification, MET overexpression, and MET fusion. Furthermore, challenges and hurdles underlying these common detection platforms are discussed.