Cancer reports最新文献

Background

PD-L1 expression in tumors and immune cells is a biomarker for the efficacy of anti-PD-1 antibody (APA) therapy across diverse cancers. Based on the results from the KEYNOTE-048 trial, pembrolizumab monotherapy is indicated for platinum-sensitive recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC) with a positive combined positive score (CPS). Conversely, nivolumab is utilized for platinum-pretreated R/M-HNSCC regardless of the positive tumor proportion score (TPS) following the results of the CheckMate-141; however, its subgroup analysis indicated that TPS-positive population tended to have a relatively high overall response rate and progression-free survival (PFS). Although, the superior PD-L1 evaluation method for predicting APA therapy efficacy in R/M-HNSCC and the appropriate cut-off value remain undetermined. This study aims to elucidate the relationship between short-term outcomes and PD-L1 expression based on CPS and TPS in R/M-HNSCC patients undergoing APA monotherapy.

Methods

R/M-HNSCC patients receiving APA monotherapy from 2018 to 2021 with available samples were enrolled. An experienced pathologist evaluated CPS and TPS utilizing the PD-L1 IHC 22C3 pharmDx assay. Short-term outcomes were assessed by clinical benefit rate (CBR), objective response rate (ORR), and PFS.

Results

Fifty-three R/M-HNSCC patients received APA monotherapy. Forty-seven had CPS ≥ 1, and 44 had TPS ≥ 1%. By receiver-operating characteristic curve analysis, the CPS cut-off value for predicting better CBR was determined to be 50. The ORR/CBR tended to be higher when CPS was positive. Although differences in PFS were not observed for a cut-off value of 1 or 20, they were observed for 50 (3.2 vs. 8.4 months; hazard ratio 0.44, p = 0.02). ORR and CBR were respectively 12.5% and 12.5% in the TPS < 1% group and 33.3% and 48.9% in the ≥ 1% group. The TPS < 1% group showed significantly poorer PFS (1.9 vs. 4.5 months, hazard ratio 0.40, p = 0.01).

Conclusion

The short-term efficacy of APA monotherapy in R/M-HNSCC patients tended to be better when CPS was positive. TPS helps predict the population that does not benefit from APA monotherapy.

Background

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. JAM2, a member of the Junctional adhesion molecule (JAM) family, plays diverse roles in cell–cell contacts and tumor development. Although JAM2's expression and functions have been reported in various cancers, its clinical and biological significance in LUAD remains unclear.

Aims

The aim of this study was to investigate the expression and function of JAM2 in LUAD, and to assess its potential as a prognostic gene and a molecular target for early diagnosis and targeted therapy.

Materials

Immunohistochemistry (IHC) was performed on 37 pairs of LUAD tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted among co-expression genes in different JAM2 subgroups. In vitro experiments were also conducted to study the migratory and invasive capabilities of LUAD cells when JAM2 was overexpressed.

Results

The study confirmed that JAM2 was downregulated in LUAD, possibly due to methylation. JAM2 emerged as an independent prognostic gene for predicting the outcomes of patients with LUAD. IHC analysis revealed the significance of JAM2 with clinicopathological parameters in LUAD. GO and KEGG analyses provided insights into the biological processes and pathways associated with JAM2. In vitro experiments showed that overexpressing JAM2 significantly suppressed the migratory and invasive capabilities of LUAD cells. Additionally, JAM2 played a crucial role in LUAD inflammatory infiltration, and higher JAM2 expression predicted a better immunotherapy response.

Conclusion

JAM2 may serve as a promising molecular target for early diagnosis and targeted therapy of LUAD. Its downregulation in LUAD, potential role as a prognostic gene, and influence on cell migration, invasion, and inflammatory infiltration make it a valuable target for further research and development of therapeutic strategies.

Background

Current approach to clinically suspicious biopsy-naïve men consists performing prostate MRI, followed by combined systematic (TRUS-Bx) and MRI-Ultrasound fusion biopsy (MRI-TBx) in those with PIRADS score ≥ 3. Researchers have attempted to determine who benefits from each biopsy method, but the results do not support the safe use of one method alone. This study aims to determine the optimal approach in biopsy-naïve men, according to their PSA levels.

Methods and Results

A retrospective chart review of clinically suspicious biopsy-naïve men who underwent both TRUS-Bx and MRI-TBx was done. Prostate specific antigen (PSA) levels were compared between patients only positive for MRI-TBx and those with positive TRUS-Bx. Further, cancer cases were divided to < 10 and ≥ 10 PSA groups and the pathology results, obtained by each method, were compared. Out of 195 men, 36 were diagnosed with prostate cancer (PCa). PCa was diagnosed by both MRI-TBx and TRUS-Bx in 26 men, half of whom had PSA > 10 ng/mL. At PSA ≤ 10 ng/mL, PCa would have been missed in 4 men (11.1%) had MRI-TBx not been done, and in 6 men (16.6%) had TRUS-Bx not been done.

Conclusion

Despite attempts to perform only one biopsy method in men with clinical suspicion of prostate cancer, we propose that at least in men with PSA ≤ 10 ng/mL, both systematic and MRI-targeted biopsies be performed.

Background

Changes in functional genetic polymorphisms may increase or decrease the risk of cancer in patients. Nowadays, the association between polymorphisms in the interleukin-8 (IL-8) gene and the susceptibility of cancer risk have been investigated in many studies, however, above relationships remain unclear.

Aim

The current study aims to comprehensively evaluate the association between IL-8 gene six polymorphisms and the whole cancer risk, especially −251 polymorphism and gastric cancer.

Methods and Results

Six polymorphisms (−251, −353, +678, +1633, +2767, +781) were collected. The expression of serum IL-8 was calculated by ELISA assay. First, 104 case–control studies were conducted. Second, this research has made significant discoveries regarding the −251, −353 and +781 polymorphisms and the potential associations with cancer risk. Finally, the serum IL-8 levels in gastric cancer patients with AA/TT genotypes were significantly higher than those with the same genotypes of healthy controls and TT genotypes in gastric cancer patients.

Conclusion

Overall, the investigation has revealed that IL-8 gene polymorphisms significantly influence vulnerability to cancer development, especially for gastric cancer.

Backgroud

Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with a generally dismal prognosis and no standard of care established, despite a known association with epidermal growth factor receptor 2 (HER2) and androgen receptor (AR) over-expression.

Case

We report the case of a 64-year-old female with extra- and intracranial metastases of SDC with evidence of AR and HER2 overexpression. After progression on first line chemotherapy, was administered neratinib, a pan-Erb2 receptor tyrosine kinase inhibitor.

Even with central nervous system involvement at diagnosis, a durable clinical response was obtained with a PFS of 11 months and no significant toxicities to manage. Best response observed during tratment was partial response.

Conclusions

This case confirms the potential efficacy of neratinib in HER2-positive SDC and underlines the need to define the best therapeutic sequence and potential biomarkers for these rare patients.

Introduction

With the use of immune checkpoint inhibitors (ICIs) and targeted therapies, the clinical outcomes of metastatic melanoma have drastically improved. The current scenario has reduced the use of chemotherapy as a first-line treatment. We report an interesting case of a patient with stage IV ano-rectal canal malignant melanoma with an exceptional response to single-agent temozolomide.

Case Report

We diagnosed a 55-year-old female with stage IV anorectal melanoma, BRAF V600 mutation negative. Owing to her poor performance status (PS) and non-affordability of immunotherapy, after informed decision-making, she was started on single agent, temozolomide. She achieved a complete metabolic response and sustained it for 3 years and continues to do so with the first-line single-agent temozolomide.

Conclusion

In a resource-limited setting, where access to ICIs and targeted therapies is not feasible, and in patients who fail to tolerate these therapies, oral chemotherapy continues to remain effective and is worth trying in patients with poor PS.

Objective

This study aims to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in treating small-cell lung cancer (SCLC) and determine the role of PD-1 monoclonal antibodies in improving patient outcomes.

Methods

A retrospective analysis was performed on 37 SCLC patients who received PD-1 or PD-L1 inhibitors along with chemotherapy at the First Hospital of Lanzhou University between June 2018 and June 2023. Treatment effectiveness was measured by overall response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS), utilizing chi-square and T-tests, along with Kaplan–Meier and log-rank analyses.

Results

In the PD-L1 group, 16 patients achieved partial or complete response, versus 12 in the PD-1 group, though the difference in the ORR was not statistically significant (50.0% vs. 36.8%, p = 0.308). Median survival times were 21.0 months for PD-L1 and 17.0 months for PD-1, with no statistically meaningful difference (p = 0.180). Adverse effects were comparable between the groups in terms of thyroid function (p = 0.898), but bone marrow suppression and gastrointestinal reactions were significantly less severe in the PD-L1 group (p = 0.047 and p = 0.002).

Conclusion

Immunotherapy combined with chemotherapy offers significant benefits for advanced SCLC patients, irrespective of the type of inhibitor used. Despite the higher incidence of adverse reactions with PD-1 inhibitors, they remain a viable option, particularly when PD-L1 inhibitors are not available, due to their manageable safety profile and effective response.

Background

Denosumab represents a valuable treatment option for unresectable giant cell tumors of the bone (GCTBs). However, no standardized protocols exist determining the length of administration, with few studies having been published on patients who reached the end of treatment.

Aims

To analyze the outcomes of patients diagnosed with GCTB and who had finished single treatment with denosumab.

Methods and Results

This is a multicenter, retrospective, descriptive study carried out in seven Spanish hospitals with multidisciplinary sarcoma and musculoskeletal tumor boards, between 2009 and 2019. Sixteen patients diagnosed with unresectable GCTBs and treated with denosumab who had reached the end of their treatment were recruited for the study and had been followed up for a minimum of 2 years. Fifty percent of patients discontinued denosumab after showing signs of tumor control. The disease remained stable in 69% of patients (n = 11), with a median recurrence-free survival time of 46 months (20–157 months) after being treated for a median period of 19 months (5–83 months). Four patients experienced local progression, and one presented multifocal progression. These five patients were treated for a median period of 46 months (14–76 months), with a median recurrence-free survival time of 9 months (5–25 months).

Conclusion

The findings of the present study suggest that discontinuation of denosumab in patients with unresectable GCTB is not necessarily associated with the progression of the disease. Further research is needed to determine how long denosumab should be administered to minimize the risk of recurrence.

Background

Malignant tumors release growth factors, promoting lymphangiogenesis in primary tumors and draining sentinel lymph nodes, ultimately facilitating lymph node metastasis. As a malignant lymphatic tumor entity, lymphangiosarcomas are characterized by low survival rates and limited treatment options. The transcription factor SOX18 plays a crucial role in both lymphatic endothelial cell differentiation and cancer-induced lymphangiogenesis.

Aims

In this in vitro study, we investigated the potential therapeutic effect of a small molecule called Sm4, which inhibits SOX18, on lymphatic endothelial and lymphangiosarcoma cells in vitro.

Methods and Results

Human dermal lymphatic endothelial cells (HDLECs), lymphangiosarcoma cells (MO-LAS), and other endothelial cell lines were cultured. We found that Sox18 exhibited high mRNA expression levels in both HDLEC and MO-LAS. Sm4 treatment decreased the Sox18 expression level at the mRNA and protein levels in both HDLEC and MO-LAS significantly, a phenomenon confirmed through immunofluorescence images. Additionally, Sm4 treatment suppressed the expression of key lymphatic phenotype markers (Prox1, Flt4, and Lyve1) and hindered migration in both HDLEC and MO-LAS, all while maintaining cell viability.

Conclusion

These findings suggest that targeting SOX18 with Sm4 may hold potential as a therapeutic strategy for lymphangiosarcoma and cancer-induced lymphatic metastasis. Further in vitro studies are warranted to investigate the mechanisms and conduct dose–response analyses to evaluate Sm4's potential as a targeted therapy for lymphangiosarcoma and cancer-induced lymphangiogenesis in the future.