Clinical & Translational Oncology最新文献

Colorectal cancer is one of the most common cancers worldwide. Lymph node metastasis is an important marker of colorectal cancer progression and plays a key role in the evaluation of patient prognosis. Accurate preoperative assessment of lymph node metastasis is crucial for devising appropriate treatment plans. However, current clinical imaging methods have limitations in many aspects. Therefore, the discovery of a method for accurately predicting lymph node metastasis is crucial clinical decision-making. DNA methylation is a common epigenetic modification that can regulate gene expression, which also has an important impact on the development of colorectal cancer. It is considered to be a promising biomarker with good specificity and stability and has promising application in predicting lymph node metastasis in patients with colorectal cancer. This article reviews the characteristics and limitations of currently available methods for predicting lymph node metastasis in patients with colorectal cancer and discusses the role of DNA methylation as a biomarker.

Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.

Immunotherapies, mainly immune checkpoint inhibitors (ICIs), have revolutionized cancer treatment strategies over the past decade, but their limitations have limited clinical applications. Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cell therapy (ACT), which collects infiltrating lymphocytes at the tumor site and expands them in vitro to obtain TIL final products cloned by various T-cell receptors, subsequently reinfused TIL into the patient, which is effective for the treatment of solid tumors. The approval of Lifileucel for commercialization marks the success of TIL therapy. This review summarizes the current status of clinical trials of TIL treatment. In addition, it is suggested that the current research trend of TIL should focus on improving the survival time of TIL in vivo, reducing drug toxicity, and searching for prognostic markers. Finally, it is expected that TIL therapy can be applied to a more wide range of clinical treatments.

Purpose: The tonsoku-like DNA repair protein (TONSL) encoded by the TONSL gene, located on chromosome 8q24.3, is crucial for repairing DNA double-strand breaks through homologous recombination. However, TONSL overexpression in lung adenocarcinoma (LUAD) promotes tumor development, leading to a poor prognosis.

Methods: TONSL was verified as a reliable prognostic marker for LUAD using bioinformatics, and clinical features related to LUAD prognosis were screened from the TCGA database to establish the relationship between risk factors and TONSL expression. In addition, TONSL expression in normal and LUAD tissues was verified using real-time quantitative polymerase chain reaction and immunohistochemistry. To elucidate the possible functions of TONSL, TONSL-related differentially expressed genes were screened, and functional enrichment analysis was performed. Subsequently, siRNA was used to knock down TONSL expression in lung cancer cells for cytobehavioral experiments. The effects of TONSL expression on tumor immune escape were analyzed using the ESTIMATE algorithm and tumor immune-infiltration analysis. In addition, the half-maximal inhibitory concentration of LUAD with varying TONSL expression levels in response to first-line chemotherapeutic drugs and epidermal growth factor receptor-tyrosine kinase inhibitors was analyzed for drug sensitivity.

Results: Up-regulation of TONSL in LUAD promotes the proliferation, migration, and invasion of lung cancer cells, thereby contributing to a poor prognosis. Furthermore, TONSL overexpression promotes immune escape and drug sensitivity in LUAD.

Conclusion: TONSL serves as a reliable prognostic marker for LUAD, and its up-regulation is associated with increased immune escape and drug sensitivity. These findings suggest that TONSL holds potential as a novel therapeutic target for LUAD.

Objective: To observe the clinical efficacy of Camrelizumab in patients with advanced cervical cancer who presented with resistance to initial therapy.

Methods: We retrieved data from 25 patients with advanced (stage IIA2-IV) cervical cancer who were administered a combination salvage therapy with Camrelizumab due to the poor response to initial chemotherapy. The primary outcome was objective response rate (ORR) and disease control rate (DCR), the secondary endpoints included progression-free survival (PFS) and the occurrence of adverse events. To evaluate its long-term effect on PFS, we included 64 patients diagnosed with stage IIA2-IV during the study period, who were responsive to initial radiotherapy or chemotherapy and received conventional therapy as control.

Results: Camrelizumab exhibits a high salvage treatment efficacy, with ORR of 80.0% (20/25) and DCR of 88.0% (22/25) in Camrelizumab salvage group (CS group). The PFS in CS group was significantly longer than that in control group. The median follow-up time were 18.1 and 18.3 months in the CS group and the control group, respectively, and neither achieved median PFS. The adverse event (AEs) rates in the CS and control groups were 52.0% (13/25) and 51.6% (33/64), in which the most common adverse events were myelosuppression, cutaneous capillary endothelial proliferation (CCEP), and elevated liver enzymes, and the grade of AEs was less than grade 3 in all patients.

Conclusion: Camrelizumab demonstrated promising efficacy and safety as the early salvage treatment for patients with advanced cervical cancer.

Purpose: This study aimed to confirm whether Kirsten rat sarcoma viral oncogene (KRAS) mutations affect the therapeutic efficacy of non-small cell lung cancer (NSCLC) and, if so, to explore what the possible mechanisms might be.

Methods: We retrospectively analyzed the efficacy of immunochemotherapy in KRAS-mutant NSCLC patients compared to driver-negative patients. Online data platforms were used to find immunotherapy cases, and survival analysis compared treatments' efficacy. Cytotoxicity assays measured chemosensitivity in KRAS-mutant versus wild-type NSCLC to drugs like paclitaxel, carboplatin, and pemetrexed. Bioinformatics confirmed the KRAS-SLC7A11 link and cell experiments tested SLC7A11's role in chemoresistance. Animal studies verified the antitumor effects of SLC7A11 inhibitors with chemotherapy.

Results: Patients with KRAS-mutated NSCLC have a shorter therapeutic effectiveness duration with immunochemotherapy than patients with driver gene-negative status. The efficacy of immunotherapy alone is similar between the two groups. The KRAS mutation can enhance chemoresistance by upregulating SLC7A11, and inhibiting SLC7A11 can increase the sensitivity of KRAS-mutated NSCLC to chemotherapy.

Conclusion: This study suggests that KRAS-mutant NSCLC can enhance its acquired chemoresistance by overexpressing SLC7A11, leading to poorer therapeutic outcomes. Targeting the KRAS-SLC7A11 axis could increase sensitivity to chemotherapeutic drugs, providing theoretical support for future treatment directions.

Purpose: To determine the incidence of VTE and clinical outcomes in a cohort of cancer patients and COVID-19 infection, and to establish possible predictive factors of VTE.

Methods/patients: A single-center retrospective cohort study was performed to determine the incidence of VTE and mortality in 118 cancer patients with SARS-CoV-2 infection from March to August 2020. We calculated individual Khorana Risk and CATS-MICA scores in order to evaluate their utility to identify risk of VTE or death. Continuous variables were compared using Wilcoxon or Student's T test, and categorical variables were compared using the Chi-Square or Fisher's exact text among patients with and without VTE. A Log-Rank test was performed to detect mortality differences between the groups.

Results: A total of 118 patients were included. VTE global incidence was 4.2% (n = 5), and mortality 25.4% (n = 30). Obesity (p = 0.05), recent chemotherapy (p = 0.049) and use of steroids (p = 0.006) were related to higher risk of VTE in the univariate analysis, although they were not confirmed in the multivariate analysis as independent risk factors. Statistically significant differences in all-cause, COVID-19-related and cancer-related mortality according to the Khorana risk score (KRS) were observed. CATS-MICA score (CMS) also showed statistically significant differences in mortality between low- and high-risk patients. Prediction of risk of VTE development with these scores showed a tendency towards significance.

Conclusions: In this cohort, VTE incidence was similar to previously reported in the general population with SARS-CoV-2 infection. KRS was associated with overall and specific-cause mortality, and might be a useful prognostic tool in this setting.

Objective: Wnt-induced signaling protein 1 (WISP1) and Dickkopf-1 (DKK1) are highly expressed in esophageal squamous cell carcinoma (ESCC), but no direct connection was identified between them. Phenotypic plasticity is a hallmark of ESCC. This research intended to identify the association between WISP1 and DKK1 and their roles in the phenotypic plasticity of ESCC.

Methods: Genes differentially expressed in esophageal carcinoma were analyzed in the GEO database, followed by analyses of GO and KEGG enrichment to screen the hub gene. WISP1 expression and DKK1 secretion was assessed in ESCC tissues and cells. The tumor xenograft and in vivo metastasis models were established by injecting ESCC cells into nude mice. Functional deficiency and rescue experiments were conducted, followed by assays for cell proliferation, migration/invasion, stemness, epithelial-mesenchymal transition (EMT), and apoptosis, as well as tumor volume, weight, proliferation, stemness, and lung metastasis. The binding relationship and co-expression of WISP1 and DKK1 were determined.

Results: WISP1 and DKK1 were upregulated in ESCC cells and tissues, and WISP1 was enriched in the cell stemness and Wnt pathways. WISP1 knockdown subdued proliferation, migration/invasion, EMT activity, and stemness but enhanced apoptosis in ESCC cells. WISP1 knockdown restrained ESCC growth, proliferation, stemness, and metastasis in vivo. WISP1 bound to DKK1 in ESCC. DKK1 overexpression abolished the repressive impacts of WISP1 knockdown on the malignant behaviors of ESCC cells in vitro and of ESCC tumor in vivo.

Conclusion: Knockdown of WISP1/DKK1 restrains the phenotypic plasticity in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition and stemness.

Background: Pain in cancer patients has enormous impact on their quality-of-life. Radiation therapy (RT) is a cornerstone in cancer treatment. The objective of the PREDORT study is to estimate the prevalence of pain in patients attending at Radiation Oncology (RO) Services.

Methods: A prospective, multicenter study was designed for patients treated at the RO Services of reference hospitals. Patients were seen in their initial Nursing consultation, during which key data was collected, including demographic and comorbidities data, medical history, and oncological and pain characteristics. The study has received approval from the Ethics Committee of Navarra, and all patients signed the Informed Consent.

Results: Of the 860 participating patients, 306 reported some type of pain, which implies a prevalence of 35.6%. Of them, 213 identified a cause of oncological origin. The proportion of pain was similar among sexes, but the proportion of non-cancer pain was higher among women (p < 0.05). Regarding pain intensity, the magnitude of breakthrough pain in patients with oncological pain is nearly 1 point greater than in patients with non-oncological pain (7.53 vs 6.81; p = 0.064). Cancer pain is more likely to be limiting of normal life than non-cancer pain (59% versus 38%, p < 0.001). Regarding analgesic treatment, only 60/306 patients (19.6%) were receiving strong opioids. There were 68 patients with pain without any treatment (22.2%).

Conclusions: The prevalence of pain in cancer patients referred to RO services is 35.6%, with the prevalence of exclusively oncological pain being 24.8%. Understanding and addressing oncological pain is essential to provide comprehensive care to patients.