Divergent transcriptional states and kinetics of circulating tumor-infiltrating lymphocyte repertoires with highly homologous T-cell receptor sequences in a patient during immunotherapy.

Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy.

A phase I study of the CDK4/6 inhibitor ribociclib combined with gemcitabine in patients with advanced solid tumors.

Background: Based on preclinical data showing addition of CDK4/6 inhibitors to gemcitabine was synergistic, ribociclib was evaluated in combination with gemcitabine to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT).

Methods: In this single arm multicohort phase I trial, we evaluated the safety and efficacy of ribociclib plus gemcitabine in patients with advanced solid tumors. Patients received gemcitabine intravenously on days 1 and 8 followed by ribociclib days 8-14, with treatment repeated every 3 weeks.

Tenascin-C in the early lung cancer tumor microenvironment promotes progression through integrin αvβ1 and FAK.

Pre-cancerous lung lesions are commonly initiated by activating mutations in the RAS pathway, but do not transition to lung adenocarcinomas (LUAD) without additional oncogenic signals. Here, we show that expression of the extracellular matrix protein Tenascin-C (TNC) is increased in and promotes the earliest stages of LUAD development in oncogenic KRAS-driven lung cancer mouse models and in human LUAD. TNC is initially expressed by fibroblasts and its expression extends to tumor cells as the tumor becomes invasive.

Ocular adverse events associated with antibody-drug conjugates for cancer: evidence and management strategies.

Antibody-drug conjugates (ADCs) are a fast-growing class of cancer drugs designed to selectively deliver cytotoxic payloads through antibody binding to cancer cells with high expression of the target antigen, thus reducing systemic exposure and minimizing off-target effects. However, ADCs are associated with various ocular adverse events (AEs) that may impact treatment administration and patient outcomes. In this review, we provide a summary of ocular AEs associated with approved and investigational ADCs, recommendations for the mitigation and management of ocular AEs, current guidelines and expert opinions, and recommendations for clinical practice.

Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC.

Background: Sotorasib 960 mg once daily is approved to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Sotorasib exhibits non-dose proportional pharmacokinetics and clinical responses at lower doses; therefore, we evaluated the efficacy and safety of sotorasib 960 mg and 240 mg.

Methods: In this phase 2, randomized, open-label study, adults with KRAS G12C-mutated advanced NSCLC received sotorasib 960 mg or 240 mg once daily.

Exosomal Thomsen-Friedenreich Glycoantigen: A New Liquid Biopsy Biomarker for Lung and Breast Cancer Diagnoses.

Unlabelled: Exosomes are nanosized extracellular vesicles released by cells to transport biomolecules such as proteins and RNAs for intercellular communication. Exosomes play important roles in cancer development and metastasis; therefore, they have emerged as potential liquid biopsy biomarkers for cancer screening, diagnosis, and management. Many exosome cargos, including proteins, RNAs, and lipids, have been extensively investigated as biomarkers for cancer liquid biopsy.

Patients' Preferences for Adjuvant Osimertinib in Non-Small-Cell Lung Cancer After Complete Surgical Resection: What Makes It Worth It to Patients?

Background: The ADAURA trial confirmed adjuvant Osimertinib's efficacy in EGFR-mutated Non-small-cell lung cancer (NSCLC), yet the limited mature overall survival (OS) data at approval poses a challenge. This study explores patient preferences in the absence of complete OS information, hypothesizing that disease-free survival (DFS) benefit alone may influence adjuvant Osimertinib pursuit.

Methods: At Roswell Park Comprehensive Cancer Center (Jan-Dec 2021), patients assessed for adjuvant therapy received a survey probing OS and DFS preferences.

Prolonged Disease Control Despite ALK Inhibitor Discontinuation in Advanced ALK-Positive NSCLC.

Introduction: is an oncogenic driver, seen in around five per cent of advanced non-small-cell lung cancer (NSCLC) patients, which can be targeted with anaplastic lymphoma kinase tyrosine kinase inhibitors with great response rates. Disease flare refers to sudden rapid disease worsening on tyrosine kinase inhibitors (TKI) discontinuation, which is associated with shorter survival and worse outcomes. Here, we review cases previously published in the literature where patients developed disease flares, and contrast this with our patients who had prolonged survival despite TKI discontinuation.

A Phase I Study of sequences of the CDK4/6 Inhibitor, Ribociclib Combined with Gemcitabine in Patients with Advanced Solid Tumors.

Background: Based on preclinical data showing addition of CDK4/6 inhibitors to gemcitabine is synergistic, ribociclib was evaluated in combination with gemcitabine to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT).

Methods: In this single arm multicohort phase I trial, we evaluated the safety and efficacy of Ribociclib plus Gemcitabine in patients with advanced solid tumors. Patients received Gemcitabine intravenously on days 1 and 8 followed by Ribociclib days 8-14, with treatment repeated every 3 weeks.

Tumor Characteristics and Treatment Responsiveness in Pembrolizumab-Treated Non-Small Cell Lung Carcinoma.

Pembrolizumab, a widely used immune checkpoint inhibitor (ICI), has revolutionized the treatment of non-small cell lung cancer (NSCLC). Identifying unique tumor characteristics in patients likely to respond to pembrolizumab could help the clinical adjudication and development of a personalized therapeutic strategy. In this retrospective study, we reviewed the clinical data and pathological features of 84 NSCLC patients treated with pembrolizumab.

Measuring undergraduates' understanding of the culture of scientific research as an outcome variable in research on CUREs.

Researchers who work on course-based undergraduate research experiences (CUREs) and issues related to science, technology, engineering, and math (STEM) retention have begun exploring changes in student thinking about what it means to be a scientist. To support this effort, we developed rubrics to score answers to three open-response prompts: What does it mean to think like a scientist? What does it mean to do science? and Did you do real research in your labs? The rubric development process was iterative and was based on input from the literature, experienced researchers, and early-career undergraduates. A analysis showed that the rubric elements map to 27 of 31 statements in the Culture of Scientific Research (CSR) framework, suggesting that scored responses to the three prompts can assess how well students understand what being a science professional entails.

Long-term benefit of sotorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: plain language summary.

What Is This Summary About?: This is a plain language summary of a study called CodeBreaK 100. The CodeBreaK 100 study included patients with non-small-cell lung cancer that had spread outside the lung (advanced). Lung cancer is one of the most common forms of cancer.

Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans.

Unlabelled: Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant family of autonomous retrotransposons occupying over 17% of human DNA, is epigenetically silenced in normal tissues by the mechanisms involving p53 but is frequently derepressed in cancer, suggesting that L1-encoded proteins may act as tumor-associated antigens recognized by the immune system. In this study, we established an immunoassay to detect circulating autoantibodies against L1 proteins in human blood. Using this assay in >2,800 individuals with or without cancer, we observed significantly higher IgG titers against L1-encoded ORF1p and ORF2p in patients with lung, pancreatic, ovarian, esophageal, and liver cancers than in healthy individuals.

PD-L1 Expression by RNA-Sequencing in Non-Small Cell Lung Cancer: Concordance with Immunohistochemistry and Associations with Pembrolizumab Treatment Outcomes.

Programmed cell death ligand (PD-L1) expression by immunohistochemistry (IHC) lacks sensitivity for pembrolizumab immunotherapy selection in non-small cell lung cancer (NSCLC), particularly for tumors with low expression. We retrospectively evaluated transcriptomic PD-L1 by mRNA next-generation sequencing (RNA-seq). In an unselected NSCLC patient cohort (n = 3168) tested during standard care (2017-2021), PD-L1 IHC and RNA-seq demonstrated moderate concordance, with 80% agreement overall.

Risk of Further Progression or Death Among Durable Progression-Free Survivors With Melanoma or Non-Small-Cell Lung Cancer in PD-1 Blockade Trials: Implications for Imaging Surveillance.

Purpose: Durable progression-free survivors (dPFSors) over 2 years have been reported among patients with melanoma or non-small-cell lung cancer (NSCLC) who received PD-(L)1 therapy. However, risk of progression still exists and the optimal imaging surveillance interval is unknown.

Methods: Individual patient data for progression-free survival (PFS) were extracted from PD-1 blockade clinical trials with a follow-up of at least 5 years.

Sex-Specific Effects of Body Composition on Tumor Microenvironment in Non-Small Cell Lung Cancer: Obesity, Gender, and TME in NSCLC.

Background: There exists a gap in understanding the interaction between sex and obesity on tumor microenvironment in NSCLC. We demonstrate the combined effects of sex and body composition on clinically relevant biomarkers of NSCLC immune response.

Methods: A cohort of 409 patients with NSCLC was subdivided into 4 groups jointly defined by body mass index (BMI; cutoff of 25 kg/m2) and sex (male-high BMI, male-low BMI, female-high BMI, female-low BMI).

Fluctuations in Gut Microbiome Composition During Immune Checkpoint Inhibitor Therapy.

Background: Immune checkpoint inhibitors (ICIs) such as programmed cell death protein-1 (PD-1) inhibitors or PD-1 ligand-1 (PD-L1) inhibitors have led to remarkable improvement in outcomes of non-small cell lung cancer (NSCLC). Unfortunately, the significant benefits of ICI therapy are frequently limited by resistance to treatment and adverse effects, and the predictive value of pre-treatment tumor tissue PD-L1 expression is limited. Development of less invasive biomarkers that could identify responders and non-responders in early on-treatment could markedly improve the treatment regimen.

Survival Benefit of Perioperative Systemic Chemotherapy for Patients With N0 to N1 NSCLC Having Synchronous Brain Metastasis.

Introduction: In stage IV NSCLC with solitary or oligometastatic brain metastasis, surgical resection of the primary and definitive management of the brain metastasis is an accepted standard. However, the effect of systemic chemotherapy after surgical resection on overall survival is not well-established.

Methods: We used the National Cancer Database to retrospectively identify individuals with NSCLC as the primary tumor along with synchronous brain metastases who underwent thoracic resection with or without adjuvant chemotherapy.

Simultaneous Detection of Tumor Derived Exosomal Protein-MicroRNA Pairs with an Exo-PROS Biosensor for Cancer Diagnosis.

Tumor derived exosomes (TEXs) have emerged as promising biomarkers for cancer liquid biopsy. Conventional methods (such as ELISA and qRT-PCR) and emerging biosensing technologies mainly detect a single type of exosomal biomarker due to the distinct properties of different biomolecules. Sensitive detection of two different types of TEX biomarkers, i.

Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100.

JCO In the longest follow-up, to our knowledge, for a KRAS inhibitor, we assessed the long-term efficacy, safety, and biomarkers of sotorasib in patients with G12C-mutated advanced non-small-cell lung cancer (NSCLC) from the CodeBreaK 100 clinical trial (ClinicalTrials.gov identifier: NCT03600883). This multicenter, single-group, open-label phase I/phase II trial enrolled 174 patients with G12C-mutated, locally advanced or metastatic NSCLC after progression on prior therapies.

Predictive and Prognostic Implications of Circulating CX3CR1 CD8 T Cells in Non-Small Cell Lung Cancer Patients Treated with Chemo-Immunotherapy.

Unlabelled: Lack of reliable predictive biomarkers is a major limitation of combination therapy with chemotherapy and anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) therapy (chemo-immunotherapy). We previously observed that the increase of peripheral blood CD8 T cells expressing CX3CR1, a marker of differentiation, correlates with response to anti-PD-1 therapy; however, the predictive and prognostic value of T-cell CX3CR1 expression during chemo-immunotherapy is unknown. Here, we evaluated the utility of circulating CX3CR1CD8 T cells as a predictive correlate of response to chemo-immunotherapy in patients with non-small cell lung cancer (NSCLC).