Dan J. Raz

Targeting USP22 reprograms the tumor microenvironment and sensitizes KRAS/p53-driven lung cancer to anti-PD-1 immunotherapy

Keqiang Zhang, Ching Ouyang, Jonathan Castillo, Jinhui Wang et autres

Rationale: Ubiquitin-specific peptidase 22 (USP22), a deubiquitinase and component of the "Death-from-Cancer" 11-gene signature, is overexpressed in multiple malignancies and linked to recurrence, therapy resistance, and poor prognosis. Its role in KRAS/p53-driven lung cancer and the response to immune checkpoint inhibitors (ICIs) …

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Identification of β-Lapachone as a Potent USP22 Inhibitor That Suppresses Cancer Stemness and Enhances Chemosensitivity in Lung Adenocarcinoma

Gao Y, Keqiang Zhang, Wendong Li, J. Liu et autres

Ubiquitin-specific protease 22 (USP22) regulates epigenetic gene expression by deubiquitinating histone H2B (H2Bub1) and upregulating oncogenic proteins and pathways, while antagonizing p53-mediated tumor suppression. USP22 is frequently overexpressed in cancers and associated with therapy resistance and poor prognosis yet remains largely untargeted …

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Abstract 2909: Targeting USP22 reprograms the tumor microenvironment and sensitizes KRAS-mutant, TP53-Null Lung cancer to immunotherapy

Keqiang Zhang, Ching Ouyang, jinhui Wang, Wendong Li et autres

Abstract Ubiquitin-specific peptidase 22 (USP22), a deubiquitinase and component of the “Death-By-Cancer” gene signature, is overexpressed in many cancers and associated with recurrence, therapy resistance, and poor prognosis. Although USP22 has recently been implicated in tumor immune evasion, its role in KRAS-driven …

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Abstract 1885: USP7 inhibitor synergistically enhanced the anticancer effect of the KRAS G12C inhibitor by effectively countering feedback signaling pathways.

Yuanyuan Gao, Keqiang Zhang, Wendong Li, Chunxia Su et autres

Abstract Background: KRAS mutations are the most frequent oncogenic drivers in non-small cell lung cancer (NSCLC), with the KRAS G12C variant accounting for nearly half of KRAS-mutant cases. While KRAS inhibitors show strong antitumor activity, their efficacy is often limited by adaptive …

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Abstract 7031: Intra-tumoral Porphyromonas gingivalis mediates osimertinib resistance in EGFR-mutant lung adenocarcinoma through gingipain-mediated IGF1R activation.

Wendong Li, Mahima Chandrakant Raul, Keqiang Zhang, Jan Potempa et autres

Abstract Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the main therapy for advanced EGFR-mutant lung adenocarcinoma LUAD, but treatment response varies widely and options are limited once resistance develops. Mechanisms of primary EGFR-TKI resistance remain inadequately understood. We found …

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Abstract 2093: Elucidating the mechanistic connection between the elevated occurrence of EGFR mutation in Hispanic/Latinx lung adenocarcinoma patients.

Jonathan Castillo, William D. Wallace, Leonidas Arvanitis, Dan J. Raz et autres

Abstract Hispanic/Latinx (H/L) patients with lung adenocarcinoma have higher rates of epidermal growth factor receptor (EGFR) mutation than those who identify as non-H/L White. Although the overall survival outcome of H/L patients is better than non-H/L White patients, the subset of H/L …

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Intratumoral Bacteria Activate IGF1R Bypass Signaling to Blunt EGFR- and ALK-Inhibitor Response in Lung Cancer Cells

Aviva Rotter Maskowitz, Wendong LI, Dan J. Raz, See PDF

Chryseobacterium indologenes mediates resistance to osimertinib by activating the IGF1R pathway in EGFR-mutant lung adenocarcinoma

Wendong Li, Keqiang Zhang, M. Luque Raúl, Aviva Rotter-Maskowitz et autres

Introduction: Lung cancers harboring sensitizing epidermal growth factor receptor (EGFR) mutations typically exhibit an initial response to osimertinib; however, the development of resistance is inevitable, and there are currently no approved targeted therapies available once resistance emerges. Accumulating evidence indicates that intra-tumoral …

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Osimertinib induces reversible cardiac dysfunction through the GATA4-MYLK3-MYL2 axis

Kai Zhang, Alyssa Ayala, Ignacio Norambuena‐Soto, Vertica Agnihotri et autres

BACKGROUND AND AIMS: Osimertinib is a third-generation tyrosine kinase inhibitor targeting activating mutations of epidermal growth factor receptor with remarkable therapeutic efficacy against non-small cell lung carcinoma. However, its use has been limited by associated cardiotoxicity, primarily with heart failure. Herein, this …

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Implementing a Lung Cancer Detection and Navigation Program in the Antelope Valley: Improving Timeliness, Utilization, and Outcomes in a Low-resource Community

Dan J. Raz, Africa Robison, J. Mark Erfe, Christy Monteith et autres

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Abstract A004: Lived experiences and systemic barriers in lung cancer surgery: Perspectives from caregivers, clinicians, and administrators on social determinants of health

Dede Teteh, Madeleine Love, Aldenise P. Ewing, Betty Ferrell et autres

Abstract Background: Social Determinants of Health (SDoH) significantly influence outcomes across the cancer care continuum. However, systematic identification and integration of social risk factors into care remain limited. Understanding the perspectives of key stakeholders is essential to inform effective SDoH integration in …

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Insights from a Patient-Centered Lung Cancer Navigation Program in a Low-Resource Community

Tanyanika Phillips, Africa Robison, Jeffrey Mark Erfe, Dan J. Raz

Barriers to cancer care, including transportation and Internet insecurity, are of special concern in low-resource communities. A patient-centered, telehealth-based, barrier-focused lay navigator program may mitigate such barriers. We share insights from a quality improvement project wherein we developed and delivered a lay …

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