A5100378537- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Cancer Immunotherapy and Biomarkers
- Colorectal Cancer Treatments and Studies
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Advanced Breast Cancer Therapies
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Cancer-related Molecular Pathways
- Genetic factors in colorectal cancer
- PI3K/AKT/mTOR signaling in cancer
- Peptidase Inhibition and Analysis
- Cancer therapeutics and mechanisms
- Chronic Lymphocytic Leukemia Research
- Ferroptosis and cancer prognosis
- Immune Cell Function and Interaction
- Lung Cancer Diagnosis and Treatment
- Protease and Inhibitor Mechanisms
- Immunotherapy and Immune Responses
- Head and Neck Cancer Studies
- Ubiquitin and proteasome pathways
The University of Texas MD Anderson Cancer Center
2016-2025
Baylor College of Medicine
2013-2025
Qingdao University
2024-2025
Affiliated Hospital of Qingdao University
2024-2025
Yunnan Agricultural University
2021-2025
Peking University Third Hospital
2013-2025
Nanfang Hospital
2010-2025
Peking University
2006-2025
Southern Medical University
2010-2025
Fudan University Shanghai Cancer Center
2024
Abstract KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine efficacy PD-1 inhibitors these subgroups. Objective response rates to blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) (P < 0.001) Stand Up To Cancer (SU2C) cohort (174 patients) with LUAC patients treated nivolumab CheckMate-057 phase III...
Significance We describe the development of a small molecule that mediates degradation bromodomain and extra-terminal (BET) proteins its application in treatment castration-resistant prostate cancer (CRPC). Few therapeutic options exist to treat CRPC, especially CRPC tumors expressing constitutively active androgen receptor (AR) splice variants lack ligand-binding domain can effect androgen-independent transactivation target genes. Importantly, we demonstrate targeted BET using...
Abstract Despite recent advances in the use of immunotherapy, only a minority patients with small cell lung cancer (SCLC) respond to immune checkpoint blockade (ICB). Here, we show that targeting DNA damage response (DDR) proteins PARP and kinase 1 (CHK1) significantly increased protein surface expression PD-L1. or CHK1 inhibition remarkably potentiated antitumor effect PD-L1 augmented cytotoxic T-cell infiltration multiple immunocompetent SCLC vivo models. CD8+ depletion reversed effect,...
The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we conducted comprehensive genomic analysis gene expression, copy number, methylation, point mutations OSCC. Integrated revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cycle, TP53) two additional key genes (FAT1,...
Abstract STK11/LKB1 is among the most commonly inactivated tumor suppressors in non–small cell lung cancer (NSCLC), especially tumors harboring KRAS mutations. Many oncogenes promote immune escape, undermining effectiveness of immunotherapies, but it unclear whether inactivation suppressor genes, such as STK11/LKB1, exerts similar effects. In this study, we investigated consequences loss on microenvironment a mouse model KRAS-driven NSCLC. Genetic ablation resulted accumulation neutrophils...
Abstract Small cell lung cancer (SCLC) is an aggressive malignancy distinct from non–small (NSCLC) in its metastatic potential and treatment response. Using integrative proteomic transcriptomic analysis, we investigated molecular differences contributing to the clinical behavior of SCLCs NSCLCs. showed lower levels several receptor tyrosine kinases decreased activation phosphoinositide 3-kinase (PI3K) Ras/mitogen-activated protein (MAP)/extracellular signal–regulated kinase (ERK) (MEK)...
Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) play a critical role cancer cell growth and resistance to therapy. Most mutations occur at codons 12 13. In colorectal cancer, presence of any mutant KRas amino acid substitution is negative predictor patient response targeted However, non–small lung (NSCLC), evidence that KRAS mutation predictive factor conflicting. We used data from molecularly clinical trial for 215 patients with tissues available out 268...
We previously demonstrated the association between epithelial-to-mesenchymal transition (EMT) and drug response in lung cancer using an EMT signature derived cell lines. Given contribution of tumor microenvironments to EMT, we extended our investigation patient tumors from 11 types develop a pan-cancer signature.Using signature, conducted integrated, global analysis genomic proteomic profiles associated with across 1,934 including breast, lung, colon, ovarian, bladder cancers. Differences...
Abstract PROteolysis-TArgeting Chimeras (PROTACs) are hetero-bifunctional molecules that recruit an E3 ubiquitin ligase to a given substrate protein resulting in its targeted degradation. Many potent PROTACs with specificity for dissimilar targets have been developed; however, the factors governing degradation selectivity within closely-related families remain elusive. Here, we generate isoform-selective p38 MAPK family using single warhead (foretinib) and recruited (von Hippel-Lindau)....
Abstract Purpose: Promising results in the treatment of non–small cell lung cancer (NSCLC) have been seen with agents targeting immune checkpoints, such as programmed death 1 (PD-1) or ligand-1 (PD-L1). However, only a select group patients respond to these interventions. The identification biomarkers that predict clinical benefit checkpoint blockade is critical successful translation agents. Methods: We conducted an integrated analysis three independent large datasets, including Cancer...
Abstract Although treatment with immune checkpoint inhibitors provides promising benefit for patients cancer, optimal use is encumbered by high resistance rates and requires a thorough understanding of mechanisms. We observed that tumors treated PD-1/PD-L1 blocking antibodies develop through the upregulation CD38, which induced all-trans retinoic acid IFNβ in tumor microenvironment. In vitro vivo studies demonstrate CD38 inhibits CD8+ T-cell function via adenosine receptor signaling or...
Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients Methods A total 104 patients with recurrent SCLC were randomly assigned 1:1 oral or placebo 40 mg twice daily, days 1 7, 150 200 mg/m
Significance A significant proportion of head and neck cancer is driven by human papillomavirus (HPV) infection, the expression viral oncogenes involved in development these tumors. However, role HPV integration primary tumors beyond increasing oncoproteins not understood. Here, we describe how impacts host genome amplification disruption tumor suppressors as well driving inter- intrachromosomal rearrangements. Tumors that do have integrants display distinct gene profiles DNA methylation...
Abstract Tumor extracellular matrix has been associated with drug resistance and immune suppression. Here, proteomic RNA profiling reveal increased collagen levels in lung tumors resistant to PD-1/PD-L1 blockade. Additionally, elevated correlates decreased total CD8 + T cells exhausted cell subpopulations murine human tumors. Collagen-induced exhaustion occurs through the receptor LAIR1, which is upregulated following CD18 interaction collagen, induces SHP-1. Reduction tumor deposition LOXL2...
Abstract The androgen receptor is a major driver of prostate cancer and inhibition its transcriptional activity using competitive antagonists, such as enzalutamide remains frontline therapy for management. However, the majority patients eventually develop drug resistance. We propose that targeting degradation via Proteolysis Targeting Chimeras (PROTACs) will be better therapeutic strategy signaling in cells. Here we perform head-to-head comparison between currently approved antagonist...