Oncology Reviews最新文献

Fibroblast Activation Protein (FAP) has emerged as a critical player in cancer biology, particularly in shaping the tumour microenvironment (TME) and influencing immunotherapy outcomes. FAP-positive cancer-associated fibroblasts (CAFs) play multiple roles in tumour progression and immune modulation. FAP, predominantly expressed on CAFs, contributes significantly to extracellular matrix remodelling, angiogenesis, and the creation of an immunosuppressive milieu. There are complex interactions between FAP-positive CAFs and various components of the immune system, highlighting their impact on T cell function and macrophage polarisation. This makes FAP a promising target for cancer therapy and potentially as a biomarker for immunotherapy treatment response. This review highlights the clinical challenges to target FAP and also addresses the heterogeneity of CAFs with the need for more refined characterisation to enhance therapeutic strategies and future research directions.

MET, a receptor tyrosine kinase proto-oncogene and the specific receptor for hepatocyte growth factor (HGF), plays a critical role in the initiation and progression of osteosarcoma (OS) through sustained pathway activation. Aberrant activation of MET has been shown to trigger multiple downstream signalling pathways, including RAS-ERK, PI3K-AKT, and STAT3, which are essential for OS cell proliferation, invasion, differentiation, and drug resistance. In recent years, significant progress has been made in the development of small-molecule inhibitors and specific antibodies targeting MET for OS therapy. The use of combination therapy as a treatment strategy involves the use of MET inhibitors in conjunction with chemotherapy, immunotherapy, and other targeted therapies. This approach has the potential to overcome resistance and improve therapeutic efficacy. This review summarises the mechanisms of MET signalling in OS, with a focus on the progress of MET-targeted therapies and their combination with other therapeutic strategies. The study provides valuable insights into future research directions, offering novel perspectives on the role of MET as a therapeutic target in OS.

Background: This study analyzed the nongenetic risk factors that contributed to colorectal cancer (CRC) incidence in the South Sulawesi population through a case-control study.

Methods: The sample consisted of 89 cases and 84 controls, aged between 19-86, with 99 males and 74 females from different ethnic groups. Univariate analysis was carried out using chi-square, Fisher's exact test, $t$ -test, and Mann-Whitney U test. Significant nongenetic risk factors were selected through the logit model L1 regularization, adjusted for age, gender, and ethnicity. The analyzed risk factors were the patient's weight, height, body mass index (BMI), defecation location, exercise habit, smoking habit, marital status, occupation, education level, and distance to the nearest health center. The estimated odds ratio from the logit model was used to analyze the significance of the selected risk factors.

Results: The significant risk factors from the logit model were smoking habit, education level, marital status, distance to the nearest health center, and weight. CRC cases were more likely to have lower education (OR = 1.819, 95% CI 1.354-2.443), residing in remote areas (OR = 1.44, 95% CI 1.17-1.772), experiencing decreasing weight (OR = 1.03, 95% CI 1.013-1.048). Controls were more likely to be non-smokers (OR = 0.325, 95% CI 0.149-0.707) and unmarried (OR = 0.161, 95% CI 0.036-0.716).

Conclusion: The study determined that other nongenetic risk factors, including education level, distance to the nearest health center, weight, smoking habit, and marital status, contributed to the CRC incidence within the South Sulawesi population. The study emphasized the importance in accounting for these risk factors for further, targeted CRC preventions.

Lynch syndrome (LS) is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) genes. These mutations result in frameshift alterations, leading to the accumulation of errors within microsatellites. Individuals with LS have an elevated risk of developing colorectal and distant malignancies, including endometrial cancer (EC), which is one of the most common cancer associated with LS. Despite its significance, the association between EC and LS is often underexplored. Given the slow progression of colorectal cancer (CRC), there is an opportunity for early detection and intervention, which can aid in reducing both incidence and mortality through the identification and management of pre-malignant lesions and early-stage tumors in colorectum/endometrium. Recognizing individuals with a heightened risk of CRC is essential for implementing personalized screening strategies. This review summarizes the original research work on LS to find out the correlation of CRC following an endometrial cancer diagnosis in individuals with MMR gene mutations, may involve refine treatment strategies and moreover this review may help clinicians and researchers to get an up-to date information on LS and its advanced treatment possibilities.

Colorectal cancer is a leading cause of cancer related deaths among patients worldwide, necessitating the development of more effective and tolerable therapies. Topoisomerase I inhibitors such as Irinotecan are integral components of chemotherapy regimens used in the management of colorectal, as well as esophageal, gastric, biliary tract, pancreatic, neuroendocrine, small bowel and anal carcinomas. Efficacy and toxicity of these regimens are however impacted by metabolism via the UGT1A1 pathways. This literature review provides a comprehensive overview of UGT1A1 polymorphism in patients with colorectal cancer, including recent developments and the future landscape. Recent literature elucidating the roles of oncogenes and predictive biomarkers on anti-cancer drugs and UGT1A1 genotypes are described. The lack of consensus in the clinical management of patients with colorectal cancer were also explored in depth. A comprehensive search was performed in multiple databases (including PubMed, Embase, Web of Science, Scopus, Research gate, and Google Scholar) to identify relevant articles published up to January 2024. A total of 79 clinical studies were included in this review. The epidemiology and frequency of UGT1A1 genes polymorphisms by race, gender, ethnicity, geographic location and stage of the cancer were correlated with drug metabolism, toxicity, and survival outcomes. The tole of UGT1A1 as a prognostic and predictive biomarker, including existing challenges in clinical application were also discussed extensively.

Mitochondrial "powerhouses" play a central function in cellular metabolism and energy generation. Their dysregulation is directly correlated with a myriad of diseases, among them cancer. The serine protease ClpP, accompanied by its cochaperone ClpX, is a principal homeostatic regulator in mitochondrial function by degrading aberrant proteins in order to preserve mitochondrial integrity. Recently, evidence suggests ClpP is overexpressed in many cancer cells and, as such, is an appealing target for drug therapy. In this review, current information about the structure, physiological function, and therapeutic promise of mitochondrial ClpP in oncology is summarized. We provide an overview about the mechanistic rationale behind ClpP agonists as novel anticancer drugs, their regulation in cell signal transduction, and the major challenge in the creation of small molecules that specifically activate human ClpP, but not bacterial ClpP. The review highlights the therapeutic promise of ClpP agonists as a novel approach in cancer therapy, presenting their prospective potential for cancer treatment by focusing on an unexplored mitochondrial target.

Background: An updated meta-analysis was conducted to evaluate the efficacy of radiotherapy in rectal cancer patients treated with total mesorectal excision (TME) or other types of surgery (non-TME-only).

Methods: The PubMed, Cochrane Library, and CNKI databases were searched. Data on overall survival (OS) were extracted.

Results: Hazard ratios (HRs) for OS associated with preoperative radiotherapy, preoperative long-course concurrent chemoradiotherapy (LCCRT), preoperative radiotherapy alone, and postoperative radiotherapy in patients treated with TME were 1.02 [95% CI: 0.92-1.14, P = 0.65], 1.04 [95% CI: 0.93-1.16, P = 0.47], 0.87 [95% CI: 0.61-1.25, P = 0.46], and 1.18 [95% CI: 0.91-1.52, P = 0.20], respectively. HRs for OS associated with preoperative radiotherapy, preoperative LCCRT, preoperative radiotherapy alone, preoperative long-course RT (LCRT), and preoperative short-course radiotherapy (SCRT) in patients treated with non-TME-only surgery were 0.85 [95% CI: 0.79-0.90, P < 0.00001], 0.77 [95% CI: 0.63-0.94, P = 0.009], 0.86 [95% CI: 0.80-0.92, P < 0.0001], 0.83 [95% CI: 0.73-0.95, P = 0.005], and 0.84 [95% CI: 0.77-0.91, P= <0.0001], respectively. The HR for postoperative radiotherapy in patients treated with non-TME-only surgery was 1.08 [95% CI: 0.84-1.39, P = 0.57].

Conclusion: Preoperative radiotherapy, regardless of the regimen, improves the OS in patients treated with non-TME-only surgery, but not in those treated with TME. Postoperative radiotherapy does not improve OS.

Advances in knowledge: This meta-analysis will serve as a reference for decision-making in multidisciplinary approaches for rectal cancer patients.

Introduction: Since Röntgen's discovery of X-rays in 1895, advancements in radiobiology have significantly shaped radiotherapy practices. This historical review traces the evolution of radiobiological theories and their impacts on current therapeutic strategies.

Materials and methods: Databases such as PubMed were utilized to trace the evolution of concepts in radiobiology.

Results/discussion: One of the first theories concerning the effect of radiation was Dessauer's target theory, introduced in the 1920s. He found that damage to critical molecular cellular targets leads to cell death. In the early 20th century, Muller contributed to the understanding of DNA structure and radiation-induced mutations, highlighting theories on the impact of radiation on genetic material and cellular damage. In 1972, Kellerer and Rossi introduced the theory of dual radiation action, which explains that ionizing radiation induces sequential damage to DNA, starting with single-strand breaks and progressing to irreparable double-strand breaks. Recent advances have enhanced the understanding of the effects of radiation on the microenvironment and immune responses, thereby improving therapeutic outcomes. The significance of the sigmoid dose-response curve and the initial shoulder effect were recognized early, leading to theoretical models such as the multitarget single-hit, linear-quadratic and repair-misrepair models. The history of fractionation and the 4R/5R principles have informed today's ultrahigh fractionation techniques, including single doses of approximately 20 Gy.

Conclusion: Although significant advances have been made toward understanding the effects of radiation on cancerous and healthy tissues, many clinical observations, such as the effects of very high doses or FLASH therapy, remain poorly understood.

The Endocannabinoid System (ECS) plays a critical role in maintaining physiological homeostasis, influencing a range of processes such as neuroprotection, inflammation, energy metabolism, and immune responses. Comprising cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and degradation, the ECS has attracted increasing attention in cancer research. Cannabinoid receptor activation has been associated with the regulation of cancer-related processes, including cell proliferation, apoptosis, and angiogenesis, suggesting that the ECS may have a role in tumor progression and cancer treatment. Preclinical studies have shown that cannabinoids, through their interaction with CB1 and CB2 receptors, can inhibit tumor cell growth, induce programmed cell death, and suppress the formation of new blood vessels in various cancer models. Despite these encouraging findings, the clinical translation of ECS-targeted therapies remains in its early stages. The complexity of tumor heterogeneity, the variability in patient responses, and the challenges associated with the pharmacokinetics of cannabinoids are significant obstacles to the broader application of these findings in clinical settings. This review provides an overview of the current understanding of the ECS's involvement in cancer biology, focusing on key mechanisms by which it may influence carcinogenesis. Additionally, we discuss the therapeutic potential of targeting the ECS in cancer treatment, while highlighting the limitations and uncertainties that need to be addressed through ongoing research.

The high incidence and mortality rates associated with gastrointestinal cancers represent a significant global health challenge. In recent years, CAR T cell therapy has emerged as a promising immunotherapeutic approach, demonstrating favorable clinical outcomes. However, the application of traditional CAR T cell therapy in gastrointestinal cancers faces numerous challenges, including the suppressive tumor microenvironment and limitations in anti-tumor efficacy. The application of engineered bacteria offers a novel strategy to enhance CAR T cell therapy by modulating the tumor microenvironment and boosting immune responses, potentially leading to improved therapeutic outcomes. This review synthesizes the current research advancements related to engineered bacteria-assisted CAR T cell therapy in gastrointestinal cancers, exploring its underlying mechanisms, clinical applications, and future developmental directions.