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.

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.

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.

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.

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.