Immunotherapy for advanced-stage squamous cell lung cancer: the state of the art and outstanding questions.

Immune-checkpoint inhibitors (ICIs) have transformed the treatment paradigm for advanced-stage squamous non-small-cell lung cancer (LUSC), a histological subtype associated with inferior outcomes compared with lung adenocarcinoma. However, only a subset of patients derive durable clinical benefit. In the first-line setting, multiple ICI regimens are available, including anti-PD-(L)1 antibodies as monotherapy, in combination with chemotherapy, or with an anti-CTLA4 antibody with or without chemotherapy.

Efficacy in patients with -positive non-small-cell lung cancer treated with dacomitinib who had skin adverse events: analyses from ARCHER 1050.

We investigated association between skin adverse events (AEs) and efficacy with dacomitinib in patients with -positive non-small-cell lung cancer (NSCLC). analyses from ARCHER 1050 evaluated efficacy in patients who did and did not experience grade ≥2 skin AEs with dacomitinib. Landmark analyses were performed at 3 and 6 months.

Novel DNA Repair Inhibitors Targeting XPG to Enhance Cisplatin Therapy in Non-Small Cell Lung Cancer: Insights from In Silico and Cell-Based Studies.

NSCLC is marked by low survival and resistance to platinum-based chemotherapy. The XPG endonuclease has emerged as a promising biomarker for predicting the prognosis of cisplatin-treated patients and its downregulation having been reported to increase cisplatin efficacy. This study presents an integrated strategy for identifying small molecule inhibitors of XPG to improve cisplatin therapy in NSCLC.

Impact of the redox-active MnTnHex-2-PyP and cisplatin on the metabolome of non-small cell lung cancer cells.

Redox-based cancer therapeutic strategies aim to raise reactive oxygen species (ROS) levels in cancer cells, thus modifying their redox status, and eventually inducing cell death. Promising compounds, known as superoxide dismutase mimics (SODm), e.g.

Access to systemic treatment of non-melanoma skin cancer in Spain: a survey analysis.

Background: Novel and highly effective drugs for non-melanoma skin cancer (NMSC) improve patient outcomes, but their high cost strains healthcare systems. Spain's decentralized public health system, managed by 17 autonomous communities (AaCc), raises concerns about equitable access.

Methods: A cross-sectional survey (July-September 2023) was sent to Spanish Multidisciplinary Melanoma Group (GEM Group) members to assess access to new drugs.

Clinicopathological and molecular predictors of [F]FDG-PET disease detection in HER2-positive early breast cancer: RESPONSE, a substudy of the randomized PHERGain trial.

Background: The PHERGain study (NCT03161353) is assessing early metabolic responses to neoadjuvant treatment with trastuzumab-pertuzumab and chemotherapy de-escalation using a [Fluorine]fluorodeoxyglucose-positron emission tomography ([F]FDG-PET) and a pathological complete response-adapted strategy in HER2-positive (HER2+) early breast cancer (EBC). Herein, we present RESPONSE, a PHERGain substudy, where clinicopathological and molecular predictors of [F]FDG-PET disease detection were evaluated.

Methods: A total of 500 patients with HER2 + EBC screened in the PHERGain trial with a tumor size > 1.

Correlation between trophoblast cell-surface antigen-2 (Trop-2) expression and pathological complete response in patients with HER2-positive early breast cancer treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab.

Purpose: The prognostic and predictive role of trophoblast cell-surface antigen-2 (Trop-2) overexpression in human epidermal growth factor receptor 2-positive (HER2-positive) breast cancer is currently unknown. We retrospectively analyzed Trop-2 expression and its correlation with clinicopathologic features and pathological complete response (pCR) in HER2-positive early breast cancer (EBC) patients treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab in the PHERGain study.

Methods: Trop-2 expression at baseline was determined in formalin-fixed, paraffin-embedded primary tumor biopsies by immunohistochemistry and was first classified into expressing (Trop-2-positive) or not-expressing (Trop-2-negative) tumors.

Unveiling Novel ERCC1-XPF Complex Inhibitors: Bridging the Gap from In Silico Exploration to Experimental Design.

Modifications in DNA repair pathways are recognized as prognostic markers and potential therapeutic targets in various cancers, including non-small cell lung cancer (NSCLC). Overexpression of ERCC1 correlates with poorer prognosis and response to platinum-based chemotherapy. As a result, there is a pressing need to discover new inhibitors of the ERCC1-XPF complex that can potentiate the efficacy of cisplatin in NSCLC.

Detecting ALK, ROS1, and RET fusions and the METΔex14 splicing variant in liquid biopsies of non-small-cell lung cancer patients using RNA-based techniques.

ALK, ROS1, and RET fusions and MET∆ex14 variant associate with response to targeted therapies in non-small-cell lung cancer (NSCLC). Technologies for fusion testing in tissue must be adapted to liquid biopsies, which are often the only material available. In this study, circulating-free RNA (cfRNA) and extracellular vesicle RNA (EV-RNA) were purified from liquid biopsies.

Genomic Landscape of Primary Resistance to Osimertinib Among Hispanic Patients with EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC): Results of an Observational Longitudinal Cohort Study.

Background: Epidermal growth factor receptor (EGFR) mutations (EGFRm) represent one of the most common genomic alterations identified among patients with non-small cell lung cancer (NSCLC). Several targeted agents for patients with EGFRm have been proven safe and effective, including the third-generation tyrosine kinase inhibitor (TKI) osimertinib. Nonetheless, some patients will present with or develop EGFR-TKI resistance mechanisms.

Cabozantinib combination therapy for the treatment of solid tumors: a systematic review.

Background: Cabozantinib monotherapy is approved for the treatment of several types of solid tumors. Investigation into the use of cabozantinib combined with other therapies is increasing. To understand the evidence in this area, we performed a systematic review of cabozantinib combination therapy for the treatment of solid tumors in adults.

Durvalumab After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: Inferior Outcomes and Lack of Health Equity in Hispanic Patients Treated With PACIFIC Protocol (LA1-CLICaP).

Objectives: To compare the rate disparity between outcomes (overall survival (OS), progression-free survival (PFS), and safety) of concurrent chemoradiation (cCRT) followed by durvalumab in two patient cohorts with locally advanced (LA) stage III non-small cell lung cancer (NSCLC), one non-Hispanic White (NHW), and the other Latin-American.

Methods: A multicenter retrospective study was performed, including 80 Hispanic and 45 NHW LA stage III NSCLC patients treated with cCRT followed by durvalumab. Both cohorts were analyzed in terms of main outcomes (OS, PFS, and safety) and compared between them and with the PACIFIC trial population outcomes.

STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP).

Background: Mutations in STK11 (STK11) and, frequently co-occurring, KEAP1 mutations (KEAP1) are associated with poor survival in metastatic Non-small Cell Lung Cancer (mNSCLC) patients treated with immunotherapy. However, there are limited data regarding the prognostic or predictive significance of these genomic alterations among Hispanics.

Methods: This retrospective study analyzed a cohort of Hispanic patients (N = 103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination as first-line (Cohort A).

KRAS and MET in non-small-cell lung cancer: two of the new kids on the 'drivers' block.

Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, and therapeutic management has advanced to identify various critical oncogenic mutations that promote lung cancer tumorigenesis. Subsequent studies have developed targeted therapies against these oncogenes in the hope of personalized treatment based on the tumor's molecular genomics. This review presents a comprehensive review of the biology, new therapeutic interventions, and resistance patterns of two well-defined subgroups, tumors with KRAS and MET alterations.

JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted -Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies.

Introduction: JNJ-64041757 (JNJ-757) is a live, attenuated, double-deleted -based immunotherapy expressing human mesothelin. JNJ-757 was evaluated in patients with advanced NSCLC as monotherapy (phase 1) and in combination with nivolumab (phase 1b/2).

Methods: Patients with stage IIIB/IV NSCLC who had received previous therapy were treated with JNJ-757 (1 × 10 or 1 × 10 colony-forming units [CFUs]) alone (NCT02592967) or JNJ-757 (1 × 10 CFU) plus intravenous nivolumab 240 mg (NCT03371381).

OPALS: A New Osimertinib Adjunctive Treatment of Lung Adenocarcinoma or Glioblastoma Using Five Repurposed Drugs.

Background: Pharmacological targeting aberrant activation of epidermal growth factor receptor tyrosine kinase signaling is an established approach to treating lung adenocarcinoma. Osimertinib is a tyrosine kinase approved and effective in treating lung adenocarcinomas that have one of several common activating mutations in epidermal growth factor receptor. The emergence of resistance to osimertinib after a year or two is the rule.

Multiplex Detection of Clinically Relevant Mutations in Liquid Biopsies of Cancer Patients Using a Hybridization-Based Platform.

Background: With the advent of precision oncology, liquid biopsies are quickly gaining acceptance in the clinical setting. However, in some cases, the amount of DNA isolated is insufficient for Next-Generation Sequencing (NGS) analysis. The nCounter platform could be an alternative, but it has never been explored for detection of clinically relevant alterations in fluids.

Unmasking the expression of PD-L1 in Myeloid Derived Suppressor Cells: A case study in lung cancer to discover new drugs with specific on-target efficacy.

• PD-L1 displays variation of spatial conformation in response to phorbol ester stimulation, which may confer a critical enhancement in binding affinity. • PD-L1 conformational change may be associated with an immunoregulatory mechanism that affects therapies targeting the PD-1/PD-L1 checkpoint. • Eliminating MDSCs by promoting PD-L1 stabilized unfolded states on both PMN- and M-MDSCs could improve immunotherapy efficacy.

Tepotinib in Non-Small-Cell Lung Cancer with Exon 14 Skipping Mutations.

Background: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population.

Methods: In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed exon 14 skipping mutation.

Detection of somatic mutations in peritoneal lavages and plasma of endometrial cancer patients: A proof-of-concept study.

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Although most patients are diagnosed at early stages, 15-20% will relapse despite local treatment. Presently, there are no reliable markers to identify patients with worse outcomes who may benefit from adjuvant treatments, such as chemotherapy, and liquid biopsies may be of use in this setting.

Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions.

Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non-small-cell lung cancer and melanoma patients.