Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases.

Nearly one-fifth of patients with non-small cell Lung Cancer (NSCLC) will develop liver metastases (LMs), and the overall treatment strategy of LMs will directly affect the survival of patients. However, some retrospective studies have found that patients receiving chemotherapy or targeted therapy have a poorer prognosis once LMs develop. In recent years, multiple randomised controlled trials (RCTS) have shown significant improvements in outcomes for patients with advanced lung cancer following the introduction of immune checkpoint inhibitors (ICIs) compared to conventional chemotherapy. ICIs is safe and effective in patients with LMs, although patients with LMs are mostly underrepresented in randomised clinical trials. However, NSCLC patients with LMs have a significantly worse prognosis than those without LMs when treated with ICIs, and the mechanism by which LMs induce systemic anti-tumour immunity reduction is unknown, so the management of LMs in patients with NSCLC is a clinical challenge that requires more optimised therapies to achieve effective disease control. In this review, we summarised the mechanism of ICIs in the treatment of LMs, the clinical research and treatment progress of ICIs and their combination with other therapies in patients with LMs from NSCLC.

Elderly patients with advanced HER2-positive breast cancer with liver metastases benefit from low dose disitamab vedotin (RC48): case series and literature review.

Currently, although some antibody-drug conjugates have been shown to be safe and effective in the treatment of drug-resistant relapsed human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+ or IHC 2+/fluorescence in situ hybridization+) breast cancer, they are already approved for clinical use in China. But the clinical needs of advanced HER2-positive patients cannot be met due to adverse reactions, drug resistance, drug accessibility and other problems, thus affecting the prognosis of patients. In particular, the representation of elderly and frail patients in randomized clinical trials is significantly under-represented. We report on two elderly women with breast cancer who developed recurrent metastatic lesions after breast cancer surgery and were again confirmed HER2-positive by histopathology and immunohistochemistry. They all developed multiple metastases in the liver after second- or third-line anti-HER2 therapy. Subsequent treatment with RC48 produced good responses and tolerable adverse reactions. One patient obtained progression-free survival for more than 7 months. Based on preliminary evidence, this study shows that RC48 in HER2-positive breast cancer with liver metastases can achieve rapid remission, thereby reducing tumor load and improving patients' quality of life. In particular, RC48 has low side effects and can be well tolerated by elderly patients after dose adjustment, providing them with treatment opportunities. It needs to be further discussed in the future research.

Combination toripalimab and bevacizumab for an elderly urothelial carcinoma patient with brain metastasis who failed rapidly after radiotherapy: a case report and literature review.

Brain metastasis is a rare refractory event in patients with urothelial carcinoma. Platinum-based chemotherapy is the recommended first-line standard therapy for all metastasis urothelial carcinoma patients eligible for cisplatin or carboplatin. Patients ineligible for platinum may receive immunotherapy. No clear evidence exists that UC with brain metastasis is sensitive to immunotherapy, and the optimal treatment for patients with BM is uncertain. We evaluated the safety and efficacy of combined immunotherapy and antivascular therapy in an elderly patient with urothelial carcinoma with brain metastasis, and summarize the currently available evidence. First, she underwent a left nephrectomy and left ureterectomy and recovered well postoperatively. The postoperative pathologic findings were consistent with urothelial carcinoma. Approximately 2 years later, the patient developed impaired limb movement on the right side and underwent MRI, which revealed lesions in the left frontal lobe and suggested brain metastasis. The brain metastasis responded to local radiotherapy but progressed again in a short time. Then, the patient was administered toripalimab at 240 mg combined with bevacizumab at 300 mg every 3 weeks. After 1cycle of treatment, the patient achieved a quick response, and symptoms improved significantly. Repeat evaluation imaging demonstrated that the lesions in the brain and lung were significantly smaller and evaluation showed partial response. The treatment was well tolerated and the patient remained in partial response until the last follow-up by July 2022, 6 months after the initiation of treatment. This case suggests that immune checkpoint blockade combined with antivascular therapy might be a new possibility for patients with metastatic urothelial carcinoma, including brain metastases.

A review of research progress on mechanisms and overcoming strategies of acquired osimertinib resistance.

Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) is the standard first-line treatment for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Third-generation EGFR-TKIs, represented by osimertinib, have been approved to overcome the EGFR T790M mutation in patients who are resistant to first- or second-generation TKIs, which brings more survival benefits for patients with advanced NSCLC. However, resistance to the third generation of EGFR-TKIs is still inevitable. Acquired drug resistance is the main reason for limiting the long-term effectiveness of targeted therapy in EGFR-mutated NSCLC patients. The mechanism of EGFR-TKI resistance of the third generation has become a focus of research in the field of targeted therapy. In this review, we summarize the research progress in resistance mechanisms of advanced NSCLC to osimertinib and the potential overcoming strategies and hope to provide a clinical basis and ideas for precision treatment of NSCLC.

Tislelizumab combined with apatinib in the treatment of advanced renal clear cell carcinoma: a case report.

Most patients with advanced renal cancer develop drug resistance to targeted drugs, and the disease progresses with the prolongation of the treatment cycle. Therefore, it is necessary to explore new treatment methods for advanced renal cancer to obtain continuous efficacy and prolong the survival time of patients. The patient was diagnosed with advanced renal cancer that had progressed after previous antiangiogenic drug therapy, based on the clinical course and imaging findings. The patient was treated with 'tislelizumab plus apatinib'. The clinical discomfort symptoms were quickly relieved after treatment, and the evaluation two cycles later showed stable disease. After two cycles of continuation of the original regimen, reevaluation computed tomography demonstrated a significant reduction in the size of the abdominal cavity mass and the therapeutic evaluation was partial remission after four cycles; however, the patient developed abnormal liver function after treatment, manifested as nausea and poor appetite, and significantly increased bilirubin and transaminase levels, which were considered as immune-related liver injuries. After glucocorticoid treatment, the patient's condition quickly improved and recovered. This report is the first to suggest a potential approach to advanced renal clear cell carcinoma and describes the effects of immunocombination therapy on advanced renal clear cell carcinoma; the results showed the current stage success of the immunocombination treatment, suggesting that this treatment may be an effective treatment option for patients with advanced renal clear cell carcinoma. In addition, the toxic and side effects of combined immunotherapy need to be carefully identified by every doctor. Since only one patient with advanced renal cancer was observed in this report, the clinical data are very limited and further observation and accumulation of more experience are needed, and further clinical studies will be conducted on the efficacy and safety of this combination regimen.

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer.

More than 1.9 million new colorectal cancer (CRC) cases and 935000 deaths were estimated to occur worldwide in 2020, representing about one in ten cancer cases and deaths. Overall, colorectal ranks third in incidence, but second in mortality. More than half of the patients are in advanced stages at diagnosis. Treatment options are complex because of the heterogeneity of the patient population, including different molecular subtypes. Treatments have included conventional fluorouracil-based chemotherapy, targeted therapy, immunotherapy, etc. In recent years, with the development of genetic testing technology, more and more targeted drugs have been applied to the treatment of CRC, which has further prolonged the survival of metastatic CRC patients.

Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with brain metastases.

About 40% of patients with non-small cell lung cancer (NSCLC) develop brain metastases (BMs) throughout the disease, and the occurrence of BMs is considered to have a fairly high mortality rate. Therefore, the management of brain metastases in NSCLC patients is a clinical challenge. Currently, multidisciplinary diagnosis and treatment methods are often used to achieve effective control of intracranial disease and prolong survival. Immunotherapy (IT) is one of the core therapies for NSCLC. Single or combined IT represented by immune checkpoint inhibitors(ICIs) of programmed death-1(PD-1)/ programmed cell death-ligand 1 (PD-L1) can significantly improve the prognosis of patients with advanced NSCLC.ICIs has been shown to be safe and effective in patients with BMs, although patients with BMs are mostly underrepresented in randomized clinical trials. In this review, we summarized the mechanism of ICIs in the treatment of BMs, and the clinical research and treatment progress of ICIs and their combination with other therapies in patients with BMs s from NSCLC.

Oral Anlotinib Maintenance Therapy for an Advanced Malignant Peritoneal Mesothelioma Diagnosed by Laparoscopy After Initial Misdiagnosis to Obtain Longer Progression-Free Survival: Case Report and Literature Review.

Malignant peritoneal mesothelioma (MPeM) is a rare and highly invasive malignant tumor with a lack of specificity in clinical manifestations, which can easily lead to misdiagnosis and missed diagnosis. Due to the difficulty of early diagnosis, most patients are already in the advanced stage when diagnosed, and the prognosis is poor. At present, there is no standard treatment strategy, and the existing treatment methods are not effective, the duration of remission is short, which cannot meet the clinical needs. Here we describe a patient with advanced MPeM, initially misdiagnosed as ovarian cancer, who responded to treatment with bevacizumab in combination with albumin-bound paclitaxel and cisplatin. In preparation for cytoreductive surgery (CRS), MPeM was confirmed by laparoscopic peritoneal nodule biopsy combined with histological and immunohistochemical results. Subsequently, due to intolerable neurotoxicity after chemotherapy, she received oral anlotinib therapy on April 25, 2022, and remained stable disease (SD) with the medication, having achieved more than 14 months of progression-free survival (PFS) as of the date of our manuscript submission. The patient's total treatment time was over 19 months. These treatments delayed tumor progression, reduced drug side effects, maintained a good quality of life, and further extended overall survival (OS). Our experience is that on the one hand, it is necessary to increase the clinician's understanding of the disease, and make full use of tissue samples and immunohistochemical staining to reduce the occurrence of misdiagnosis. On the other hand, based on preliminary evidence, we found that oral anlotinib offers a viable maintenance treatment strategy for patients with advanced mesothelioma, which needs to be further explored in future studies.

Oral fruquintinib combined with tegafur-gimeracil-oteracil potassium for advanced colorectal cancer to obtain longer progression-free survival: A case report.

BACKGROUND: After the failure of second-line standard therapy, effective treatment options for metastatic colorectal cancer are limited, and the duration of remission cannot meet clinical needs. In addition, associated drug toxicity may lead to treatment interruption that may affect patient outcomes. Therefore, more safe, effective and convenient treatments are urgently needed. CASE SUMMARY: Here, we describe a patient with advanced colorectal cancer with multiple metastases in both lungs. Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment, and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression. However, treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea. He received targeted therapy with fruquintinib starting on August 26, 2020 and responded well for 12 mo. After slow progression of the lung metastases, progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy. Overall treatment duration was more than 25.5 mo. The treatments delayed tumor progression, reduced drug side effects, maintained a good quality of life, and further extended overall survival. CONCLUSION: This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.

Osteopontin promotes gastric cancer progression via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. Osteopontin (OPN) is thought to be closely related to the occurrence, metastasis and prognosis of many types of tumors. AIM: To investigate the effects of OPN on the proliferation, invasion and migration of GC cells and its possible mechanism. METHODS: The mRNA and protein expression of OPN in the GC cells were analyzed by real-time quantitative-reverse transcription polymerase chain reaction and western blotting, and observe the effect of varying degree expression OPN on the proliferation and other behaviors of GC. Next, the effects of OPN knockdown on GC cells migration and invasion were examined. The short hairpin RNA (shRNA) and negative control shRNA targeting OPN-shRNA were transfected into the cells according to the manufacturer's instructions. Non transfected cells were classified as control in the identical transfecting process. 24 h after RNA transfection cell proliferation activity was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay, and cell invasiveness and migration were detected by Trans well assay. Meanwhile, the expression of protein kinase B (AKT), matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF) in the human GC cell lines was detected by reverse transcription polymerase chain reaction and western blotting. RESULTS: The results of this study revealed that OPN mRNA and protein expression levels were highly expressed in SGC-7901 cells. OPN knockdown by specific shRNA noticeably reduced the capabilities of proliferation, invasion and migration of SGC-7901 cells. Moreover, in the experiments of investigating the underlying mechanism, results showed that OPN knockdown could down-regulated the expression of MMP-2 and VEGF, it also decreased the phosphorylation of AKT. Meanwhile, the protein expression levels of MMP-2, VEGF and phosphorylated AKT was noticeable lower than that in control group in the GC cells after they were added to phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002). CONCLUSION: These results suggested that OPN though PI3K/AKT/mammalian target of rapamycin signal pathway to up-regulate MMP-2 and VEGF expression, which contribute SGC-7901 cells to proliferation, invasion and migration. Thus, our results demonstrate that OPN may serve as a novel prognostic biomarkers as well as a potential therapeutic targets for GC.

An elderly advanced non-small cell lung cancer patient harboring rare epidermal growth factor receptor mutations L861R benefited from afatinib: A case report.

RATIONALE: Tyrosine kinase inhibitors (TKIs) have significant efficacy in patients with advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations. No clear evidence exists that EGFR-L861R is sensitive to TKIs, and the best treatment for NSCLC patients with EGFR-L861R mutation is undetermined. PATIENT CONCERNS: We report the characteristics, efficacy, and adverse events of a patient harboring rare EGFR mutations L861R treated with afatinib, and summarize the currently available evidence and ongoing clinical trials regarding it. DIAGNOSIS: The patient was diagnosed with advanced lung cancer that had progressed after previous osimertinib drug therapy, based on the clinical course and imaging findings. INTERVENTIONS: The patient underwent genetic testing, and next-generation sequencing detected rare EGFR mutations L861R in the plasma (mutation abundance 8.1%). The patient was then administered afatinib at 30 mg quaque die combined with bevacizumab at 300 mg every 2 weeks. OUTCOMES: After 1 month of treatment, the patient achieved a quick response, and symptoms improved significantly. Repeat evaluation imaging demonstrated that the lesions in the lung and brain were significantly smaller and evaluation showed partial remission. However, despite showing an initial response, the patient presented with behavioral abnormalities, headaches, and sudden confusion after 2 months, and subsequently appeared coma. The family elected to forgo further therapy due to the patient's age and enrolled in hospice care, passing 14 months after the initial diagnosis. LESSON: EGFR-L861R mutation could help predict the sensitivity of patients with advanced NSCLC to TKIs.

Effect of Bicalutamide on the proliferation and invasion of human triple negative breast cancer MDA-MB-231 cells.

Previous studies have shown androgen receptor (AR) is associated with the occurrence, development, recurrence, metastasis, and prognosis of triple negative breast cancer (TNBC). More and more experts have noticed that AR signaling pathway plays an important role in the occurrence and development of TNBC. The purpose of this study is to detect the inhibitory efficacy and mechanism of Bicalutamide on the proliferation and invasion of TNBC cells.MDA-MB-231 cells of human breast cancer cells were treated with 0, 25, 100 µmol/L of Bicalutamide, cell proliferation assay was performed to assess cell proliferation viability by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide assay and cell invasion was evaluated by Transwell assay. Meanwhile, flow cytometric analysis and western blotting were performed to investigate the mechanism of Bicalutamide on the proliferation and invasion of MDA-MB-231 cells.Bicalutamide could efficiently inhibit the proliferation and invasion of MDA-MB-231 cells in a dose-dependent manner. In addition, Bicalutamide could significantly induce the cell cycle arrest at G0/G1 phase and decrease the protein expression of AR, cyclin D1, matrix metalloprotease-2 (MMP-2), and matrix metalloprotease-9 (MMP-9).The present study indicated the Bicalutamide inhibited the proliferation and invasion process of triple negative breast cancer cells by targeting AR signaling pathway and down-regulating MMP-2/-9 protein expression levels.