A cohort-based multi-omics identifies nuclear translocation of eIF5B /PD-L1/CD44 complex as the target to overcome Osimertinib resistance of ARID1A-deficient lung adenocarcinoma.

Background: Osimertinib has emerged as a critical element in the treatment landscape following recent clinical trials. Further investigation into the mechanisms driving resistance to Osimertinib is necessary to address the restricted treatment options and survival advantages that are compromised by resistance in patients with EGFR-mutated lung adenocarcinoma (LUAD).

Methods: Spatial transcriptomic and proteomic analyses were utilized to investigate the mechanisms of Osimertinib resistance.

Conversion therapy with chemoimmunotherapy induced pCR in a stage IV lung squamous cell carcinoma patient harboring exon 20 insertion.

This case study details an innovative conversion therapy strategy in a 58-year-old Asian male with baseline stage cTNM advanced lung squamous cell carcinoma (SCC) harboring a rare exon 20 insertion mutation with concurrent high PD-L1 expression who achieved a pathologic complete response (pCR) after preoperative immunotherapy plus chemotherapy. The patient initially presented with coughing and bloody sputum and was comprehensively diagnosed via PET/CT scanning, bronchoscopic biopsy and next-generation sequencing. After four cycles of platinum‒paclitaxel chemotherapy plus immunotherapy with pembrolizumab (a PD-1 blockade), significant primary tumor shrinkage and the disappearance of oligometastasis in the right adrenal gland were discovered via CT scans.

Neoadjuvant PD-(L)1 blockade with or without chemotherapy versus chemotherapy alone in mismatch repair-deficient, potentially resectable stage III-IV gastric cancer patients: a single-center retrospective study.

Background: Currently, PD-(L)1 blockade-based neoadjuvant treatment has shown promising outcomes in patients with potentially resectable gastric cancer. In this real-world study, we aimed to retrospectively observe the efficacy including tumor response and event-free survival (EFS), and safety of PD-(L)1 blockade-based neoadjuvant treatment versus chemotherapy alone in potentially resectable gastric cancer patients with microsatellite instability-high (MSI-H) or mismatch-repair deficient (dMMR) status.

Methods: We retrospectively collected the clinical data of patients with potentially resectable gastric cancer and MSI-H/dMMR status who received neoadjuvant treatment followed by D2 gastrectomy at the Affiliated Hospital of Qingdao University from January 2019 to June 2023.

SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response.

The switch/sucrose non-fermenting (SWI/SNF) complex family includes important chromatin-remodeling factors that are frequently mutated in lung adenocarcinoma (LUAD). However, the role of one family member, SMARCA4, in LUAD prognosis and immunotherapy sensitivity remains unclear. In the present study, 6745 LUAD samples from the cBioPortal database were used to analyze the relationships between SMARCA4 mutations and patient prognoses and clinical characteristics.

Neoadjuvant PD-(L)1 blockade plus platinum-based chemotherapy for potentially resectable oncogene-positive non-small cell lung cancer.

Background: Whether programmed cell death-1/ligand-1 (PD-1/PD-L1) blockade-based neoadjuvant treatment may benefit locally advanced oncogene-mutant non-small cell lung cancer (NSCLC) patients remains controversial. This retrospective study was designed to observe the efficacy and safety of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy versus chemotherapy and corresponding tyrosine kinase inhibitors (TKIs) in patients with resectable oncogene-positive NSCLC.

Methods: Patients with potential resectable NSCLC harbouring oncogene alterations who had received neoadjuvant treatment were retrospectively recruited, and an oncogene-negative cohort of patients who received neoadjuvant PD-(L)1 blockade-based neoadjuvant treatment was reviewed for comparison during the same period.

Efficacy of immunotherapy in ARID1A-mutant solid tumors: a single-center retrospective study.

Background: Immune checkpoint inhibitors (ICIs), especially those targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have introduced a new treatment landscape for many types of tumors. However, they only achieve a limited therapeutic response. Hence, identifying patients who may benefit from ICIs is currently a challenge.

Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab.

Background: Camrelizumab, a programmed death 1 (PD-1) inhibiting antibody, has demonstrated efficacy in various malignancies and received approval in multiple countries. Despite its therapeutic benefits, camrelizumab is associated with a unique spectrum of immune-related adverse effects (irAEs), predominantly reactive cutaneous capillary endothelial proliferation (RCCEP). However, visceral manifestations of such endothelial proliferations, particularly hepatic cavernous hemangiomas, have not been extensively documented.

MET fusions are targetable genomic variants in the treatment of advanced malignancies.

Targeted therapy for malignancies has developed rapidly in recent years, benefiting patients harboring genetic mutations sensitive to relevant tyrosine kinase inhibitors (TKIs). With the development of targeted sequencing techniques, an increasing number of detectable genomic alterations in malignancies, including MET fusions, have been revealed. MET fusions, although rare among malignancies, might be functional driver genes that participate in activating downstream signaling pathways and promoting cell proliferation.

The stage-dependent prognostic role of in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death. Although novel treatment currently achieves a better response, the majority of HCC patients develop resistance and cannot benefit. Hence, novel biomarkers for guiding therapy and predicting the prognosis are needed.

Role of YES1 signaling in tumor therapy resistance.

YES proto-oncogene 1 (YES1) is an SRC family kinase (SFK) that plays a key role in cancer cell proliferation, adhesion, invasion, survival, and angiogenesis during tumorigenesis and tumor development. Reports suggest that amplification is associated with resistance to chemotherapeutic drugs and tyrosine kinase inhibitors (TKIs) in human malignancies. However, the mechanisms of drug resistance have not been fully elucidated.

RIT1 regulates mitosis and promotes proliferation by interacting with SMC3 and PDS5 in hepatocellular carcinoma.

Background: As a small G protein of Ras family, Ras-like-without-CAAX-1 (RIT1) plays a critical role in various tumors. Our previous study has demonstrated the involvement of RIT1 in promoting malignant progression of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear.

ARID1A deficiency associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes predicts a good prognosis of endometrial carcinoma.

Background: ARID1A alterations have been detected in 40% of endometrial carcinomas (ECs) and are associated with loss of its expression. The role of ARID1A in tumorigenesis and development is complex, and the prognostic role in EC remains controversial. Hence, it is of great significance to confirm the role of ARID1A in EC.

Neoadjuvant PD-1 blockade plus chemotherapy versus chemotherapy alone in locally advanced stage II-III gastric cancer: A single-centre retrospective study.

Background: PD-1 blockade has been shown to have promising efficacy and acceptable safety profiles in advanced and metastatic gastric cancer; however, the efficacy and safety of neoadjuvant PD-1 blockade-based immunotherapy plus chemotherapy in locally advanced gastric cancer (LAGC) remain uncertain.

Methods: We performed a retrospective review of patients with LAGC who received neoadjuvant treatment followed by D2 radical resection at the Affiliated Hospital of Qingdao University from 2019 to 2021. The primary aim was to investigate the difference in pathological response rates between neoadjuvant PD-1 immunotherapy plus chemotherapy and neoadjuvant chemotherapy alone.

Identification of MET fusions as novel therapeutic targets sensitive to MET inhibitors in lung cancer.

Introduction: Alterations in the MET gene, including amplifications and exon 14 skipping mutations, have been identified as actionable oncogenic alterations. However, MET fusions are rarely detected in lung cancer, and their sensitivity to therapeutics has not been systematically analyzed.

Methods: The data from 30876 lung cancer patients from the LAVA database and 7966 patients from cBioPortal database were screened.

Aberrant circulating tumor DNA methylation and exosomal microRNA biomarkers for early detection of colorectal cancer.

Introduction: Colorectal cancer (CRC) became the third most commonly diagnosed malignancy and the second leading cause of cancer death in 2020. However, the rates of early screening and early diagnosis for CRC remain unsatisfactory. Thus, it is essential to explore the initiating factors of CRC and strategies for its early diagnosis.

Optimal Treatments for NSCLC Patients Harboring Primary or Acquired Amplification.

: In non-small cell lung cancer (NSCLC) patients harboring mutations, MET-tyrosine kinase inhibitors (TKIs) have been proven to achieve a good response. However, the relative efficacy of different therapeutics in primary NSCLC patients with amplification and the treatment options for patients harboring acquired amplification after the failure of epidermal growth factor receptor (EGFR)-TKIs remain unclear. In total, 33 patients harboring primary amplification and 9 patients harboring acquired alterations identified by next-generation sequencing were enrolled.

Next-generation sequencing identifies potential novel therapeutic targets in Chinese HGSOC patients.

Background: Targeted therapy, especially the use of poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors (PARPis), has improved the outcome of patients with ovarian cancer. However, most high-grade serous ovarian cancer (HGSOC) patients have wild-type BRCA1/2, and it is necessary to disclose more potential novel targets for other available targeted drugs. So, detection of genetic alterations beyond BRCA1/2 is critical to screen HGSOC patients for personalized therapy.

Anlotinib combined with anti-PD-1 antibody, camrelizumab for advanced NSCLCs after multiple lines treatment: An open-label, dose escalation and expansion study.

Objectives: Combined therapy should be invested for those patients who are refractory to first-line therapy. Anti-angiogenic agents could enhance tumor immunity response. We designed a phase IB clinical trial and analyzed the effectiveness and safety of anlotinib combined with PD-1inhibitors Camrelizumab for multi-line pretreated and failed advanced NSCLC to explore the synergistic effect of anti-angiogenic agents and immunotherapy.

B-Cell Receptor-Associated Protein 31 Promotes Metastasis AKT/β-Catenin/Snail Pathway in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal cancer worldwide, characterized with high heterogeneity and inclination to metastasize. Emerging evidence suggests that BAP31 gets involved in cancer progression with different kinds. It still remains unknown whether and how BAP31 plays a role in HCC metastasis.

Loss of ARID1A expression promotes lung adenocarcinoma metastasis and predicts a poor prognosis.

Background: ARID1A is an essential subunit of SWI/SNF chromatin remodeling complexes. ARID1A gene mutations and loss of ARID1A expression have been observed in a variety of cancers, and to be correlated with invasion, immune escape and synthetic lethality. As yet, however, the biological effect of ARID1A expression and its role in the prognosis of lung adenocarcinoma (LUAD) patients have remained unclear.

Use tumor suppressor genes as biomarkers for diagnosis of non-small cell lung cancer.

Lung cancer is the leading cause of death worldwide. Especially, non-small cell lung cancer (NSCLC) has higher mortality rate than the other cancers. The high mortality rate is partially due to lack of efficient biomarkers for detection, diagnosis and prognosis.