Oncology Reviews最新文献

Introduction: In the last two decades, tyrosine-kinase inhibitors (TKIs) have dramatically changed the prognosis of lung and breast cancers, with significant benefits in the metastatic setting and, more recently, in the adjuvant setting for selected groups of patients. Despite their favorable oncological effects, TKIs carry a high risk for drug-drug interactions (DDIs) due to their pharmacokinetics (PK), which depend on both pH-dependent absorption and liver metabolism. However, DDIs are frequently related to "potential DDIs" (pDDIs), and their clinical relevance is often underestimated; there is also a lack of practical guidance for clinicians.

Methods and materials: We conducted a narrative review restricted to the last 20 years, involving adult individuals (aged 18 years or older) with lung or breast cancers treated with TKIs and clinical data on potential DDIs, along with reported toxicities or outcomes.

Results: We summarized the pharmacokinetic profiles and the clinical evidence of 11 TKIs used for lung or breast cancers. Moreover, we provided an easy-to-use guide to help physicians in clinical practice with recommended dose adjustments or cautions necessary to prevent severe adverse events or possible changes in TKI availability in the presence of other interfering drugs.

Conclusion: The level of evidence for DDIs during TKI treatment is low because most available data are from phase I studies in healthy volunteers and few phase II studies in cancer patients. However, since the occurrence of DDIs can be clinically significant and a prompt drug reconciliation process can be useful to prevent them, further prospective, large-sample-size clinical trials should be carried out.

Background: The landscape of oncology varies across countries and regions, and in consanguineous populations such as Saudi Arabia, the clinical management of hereditary cancers poses a distinct challenge. Hereditary breast cancer (HBC), which is a significant public health concern, accounts for approximately 5%-10% of all breast cancer cases. High-risk genes, including BRCA1, BRCA2, PALB2, TP53 and PTEN, with germline pathogenic or likely pathogenic variants (PVs/LPVs), substantially increase the risk of breast cancer and other malignancies.

Method: In this review, we explore the guidelines and the literature to present a comprehensive investigation of the genetic landscape of hereditary cancer syndromes, provide pivotal insights into disease mechanisms and inform precise clinical intervention. Given their marked therapeutic heterogeneity, a tailored precision medicine approach, rather than a uniform strategy of a one-size-fits-all model, is necessary. For high-risk breast cancer patients in Saudi Arabia, the detection rates of PVs/LPVs have reached 24%, underscoring the relevance of targeted interventions.

Results: A comprehensive framework for the management of HBCs is outlined, which focuses on consanguineous populations and adapts global guidelines. We highlight the critical roles of genetic testing in guiding personalised surveillance strategies, especially for regions where data remain limited.

Conclusion: Revealing the genetic variation associated with HBCs mitigates the burden on healthcare providers and the long-term effects of HBCs on affected individuals and their families. Moreover, it is a step ahead towards personalised prevention, treatment and intervention. This knowledge will empower research and innovation in biotechnology.

Exercise is increasingly recognized as a safe and effective adjunct therapy across the cancer care continuum, offering improvements in physiological function, psychological wellbeing, and treatment outcomes. However, conventional one-size-fits-all exercise prescriptions often fall short of addressing the diverse needs of cancer patients, who differ significantly in tumor type, treatment modality, baseline fitness, and comorbidities. Personalized exercise programs offer a tailored, evidence-informed approach that enhances safety, adherence, and clinical benefits. This narrative review synthesizes the current literature on the physiological, psychological, and oncological impacts of exercise in cancer care, emphasizing the rationale, methodologies, and emerging tools for individualized exercise prescriptions. Integration of such programs into oncology practice requires standardized assessments, interdisciplinary collaboration, and digital infrastructure, with a focus on addressing barriers to implementation and ensuring equitable access. Personalized exercise programs have the potential to improve patient outcomes and survivorship experiences across diverse cancer populations.

Cervical cancer (CeCa) remains a significant global health burden, with complex interactions between oxidative stress and immune response playing critical roles in its pathogenesis and progression. This review synthesizes current knowledge on the molecular mechanisms linking oxidative stress pathways and immune evasion, particularly focusing on human papillomavirus oncogenes E6 and E7. We highlight the dual roles of immune components such as Type 17 T helper (Th17) cells and the antioxidant enzyme superoxide dismutase 2 (SOD2), which exhibit context-dependent tumor-promoting and suppressive functions. While extensive mechanistic insights have been gained, translation to clinical practice remains limited, partly due to inconsistent biomarkers and incomplete understanding of therapeutic resistance. Recent advances in targeted therapies, including mitochondrial inhibitors, Immune checkpoint inhibitors (ICIs) (e.g., pembrolizumab, nivolumab), and PARP inhibitors, demonstrate promise but face translational hurdles such as assay variability and immune-related adverse events. Future research must address gaps including predictive biomarker development, noninvasive monitoring via liquid biopsy, and rational combination therapies integrating redox modulation and immunotherapy. Enhanced multi-omics integration and refined preclinical models are essential to advance personalized treatment strategies for CeCa.

Radiation therapy (RT) and locoregional ablation are cornerstones of modern oncology, yet their therapeutic potential is frequently limited by the challenge of sparing healthy organs-at-risk (OARs) from treatment-related complications. Temporary organ displacement (TOD) techniques directly address this issue by creating a physical separation using 'spacers' during treatment, thereby minimizing collateral damage while enhancing therapeutic precision. The clinical benefits, including improved tumor control, reduced morbidity, and enhanced survival, are documented across malignancies of the head and neck, thorax, abdomen, and pelvis. To create a unified framework for this evolving field, this comprehensive review provides a systematic classification of TOD techniques based on invasiveness, administration, device technology and the accompanying treatment mo`dality. Furthermore, we synthesize key historical and recent innovations, from non-invasive maneuvers to advanced surgical spacers, to contextualize current practices. Finally, we address barriers to standardization and highlight emerging concepts such as meta-materials, computational modeling, and digital twins, which provide promising avenues for enhancing personalized cancer care and patient outcomes.

Malignant bone tumors, particularly osteosarcoma, pose significant therapeutic challenges due to genomic heterogeneity, chemoresistance, and stagnant survival rates. The PI3K/AKT/mTOR pathway emerges as a central driver of tumor progression, metastasis, and therapeutic resistance. Everolimus (EVR), a rapamycin-derived mTORC1 inhibitor, demonstrates multifaceted antitumor effects in osteosarcoma by suppressing protein synthesis, metabolic reprogramming, angiogenesis, and osteoclastogenesis. Preclinical studies highlight EVR's synergistic potential with targeted agents (e.g., sorafenib, zoledronic acid), chemotherapy (e.g., doxorubicin), and proteasome inhibitors (e.g., bortezomib), achieving >50% tumor volume reduction and metastasis suppression in xenograft models through dual mTORC1/2 blockade, stress-apoptosis activation, and microenvironment remodeling. Clinically, phase II trials report a 45% 6-month progression-free survival (PFS) rate for EVR-sorafenib combinations in refractory osteosarcoma, albeit with manageable toxicity. Precision oncology approaches, such as EVR combined with tumor-treating fields (TTFields) and immune checkpoint inhibitors, further reveal its role in DNA repair-deficient subtypes and TME modulation. However, challenges persist, including mTORC2-mediated resistance, limited intratumoral bioavailability (<20% plasma levels), and biomarker scarcity. Future strategies emphasize bone-targeted nanoparticle delivery systems, dual-target inhibitors (e.g., RapaLink-1), and dynamic multi-omics predictive models to optimize EVR's precision. By integrating organoid platforms, AI-driven drug screening, and international trials, EVR is poised to evolve from a broad-spectrum agent into a molecularly guided therapeutic hub, bridging "anti-tumor, bone-protective, and immune-regulatory" mechanisms. This paradigm shift promises to transform osteosarcoma management from empirical combinations to biomarker-driven precision therapy, ultimately improving survival and quality of life for patients.

Breast cancer (BC) remains a leading cause of cancer-related morbidity and mortality worldwide. Its marked heterogeneity - encompassing molecular subtypes, histological characteristics, and variable therapeutic responses - continues to pose persistent clinical challenges Although advances in surgery, hormone therapy, chemotherapy, and targeted therapies have significantly improved patient outcomes, issues such as therapeutic resistance and disease relapse are still common, underscoring the need for novel molecular targets. Within this context, non-coding RNAs (ncRNAs) have emerged as pivotal regulators of breast cancer biology and hold promise as diagnostics and therapeutic agents. These non-protein-coding RNA molecules include diverse subclasses, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small non-coding RNAs (sncRNAs), each characterized by distinct structural features and biological functions. Mounting evidence implicates ncRNAs in key oncogenic processes - such as tumor initiation, progression, metastasis, immune evasion, and treatment resistance - often in a subtype-specific manner. Importantly, ncRNA expression profiles differ significantly across BC subtypes, and their stability in body fluids underscores their potential utility in liquid biopsy-based diagnostics. This review provides an integrated overview of the multifaceted roles of ncRNAs in BC, emphasizing their mechanisms of action, contributions to tumor heterogeneity, and translational potential as both biomarkers and therapeutic targets. Understanding ncRNAs complexity and context-specific functions may pave the way toward more precise, personalized interventions for BC patients.

Radiation-induced intestinal injury (RIII) poses a significant clinical challenge for patients undergoing pelvic or abdominal radiotherapy, characterized by dual features of acute symptoms (diarrhea, abdominal pain, rectal bleeding) and chronic complications (stricture, fistula, chronic pain), profoundly impacting quality of life. Despite high clinical prevalence, the molecular and cellular mechanisms underlying RIII remain poorly defined, hindering therapeutic development. Current diagnostic modalities (imaging, endoscopy) lack sensitivity and specificity for early detection or real-time monitoring. While biomarkers offer promise for non-invasive assessment and prognosis, existing candidates face limitations in reproducibility and clinical applicability. Therapeutic options, ranging from pharmaceuticals to surgery, show variable efficacy, underscoring the need for optimized strategies. This review systematically explores RIII pathogenesis, emphasizing radiation-induced immune dysregulation, epigenetic alterations, and gut microbiota dysbiosis. We discuss potential biomarkers, such as miRNA, fatty acid binding proteins (FABPs), etc. We categorize therapies into radioprotectors (pre-radiation use) and radiomitigators (post-radiation intervention), highlighting natural plant-derived compounds and traditional Chinese medicine (TCM) for their multi-target effects, alongside emerging approaches like stem cell and microbiota transplantation, with discussions on their therapeutic potential and clinical challenges. Crucially, we exclusively summarize recent clinical translation advances to accelerate drug development. Through critical evaluation of evidence, we propose future directions to refine risk stratification, enable timely intervention, and improve long-term outcomes for irradiated patients. This integrative analysis aims to bridge translational gaps and prioritize research avenues for RIII management.

Despite increases in prevalence, many cutaneous T-cell lymphoma (CTCL) patients still lack effective and safe therapies for their disease. The most prevalent subtype, mycosis fungoides is usually managed with skin directed treatments in early stages, while advanced stages are often targeted with systemic medications. These treatments are all symptomatic except for allogeneic hematopoietic stem cell transplantation, which is associated with its own risks of relapse and potentially fatal complications. A novel class of drugs termed "JAK inhibitors" (JAKi) has recently been developed primarily for chronic inflammatory diseases, but there is substantial evidence of JAK/STAT pathway overactivation also in CTCL. As of 1 December 2024, 14 JAKis have been collectively approved by the European Medicines Agency, the Food and Drug Administration and the Pharmaceutical and Medical Devices Agency of Japan. Despite some evidence from case reports, the efficacy and safety of JAKi in CTCL remains to be determined in controlled clinical trials. This review summarizes the current evidence on pathogenic JAK activation and its potential therapeutic inhibition in CTCL.

Methyltransferase-like 1 (METTL1) is a methyltransferase that modulates the RNA methylation process and has been increasingly investigated in cancer research over the past decade. The review aims to summarize the diverse roles of METTL1 in various cancers, focusing on the mechanisms underlying tumorigenesis, progression, and metastasis. Furthermore, the therapeutic value and targeting strategies for METTL1 are also discussed to provide the foundation for further development of METTL1-targeted therapies. The article integrates recent research findings to highlight significant discoveries regarding METTL1, emphasizing its potential as a therapeutic target in cancer treatment.