Publications by authors named "Ignacio I Wistuba"

Background: Genomic profiling is essential in the management of non-small cell lung cancer. However, this may often be challenging because of limited cytological tissue and extended turnaround time (TAT) for next-generation sequencing (NGS). This study aims to describe a rapid TAT workflow for molecular profiling using fine-needle aspiration (FNA) supernatants.

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Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer.

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Background: As liver metastasis is the most common cause of mortality in patients with colorectal cancer, studying colorectal cancer liver metastasis (CLM) microenvironment is essential for improved understanding of tumor biology and to identify novel therapeutic targets.

Methods: We used a multiplex immunofluorescence platform to study tumor associated macrophage (TAM) polarization and adaptive T cell subtypes in tumor samples from 105 CLM patients (49 without and 56 with preoperative chemotherapy).

Results: CLM exhibited M2 macrophage polarization, and helper T cells were the prevalent adaptive T cell subtype.

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  • The study investigates the effectiveness of perioperative chemoimmunotherapy (ChIO) in non-small cell lung cancer (NSCLC), focusing on the role of human leukocyte antigen (HLA) class I expression and loss of heterozygosity (LOH).
  • It involved 24 NSCLC patients, assessing their HLA status and integrating molecular data and clinical outcomes to understand how tumors with HLA class I defects respond to ChIO.
  • Results showed that both HLA-deficient and proficient tumors had similar rates of complete pathological response and survival, with strong immune responses observed in HLA-deficient tumors after treatment.
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  • Dual immune checkpoint blockade (ICB) using CTLA4 and PD-(L)1 inhibitors shows improved anti-tumor effectiveness and immune toxicity compared to PD-(L)1 inhibitors alone in advanced non-small-cell lung cancer (NSCLC) patients.
  • Patients with mutations in STK11 and/or KEAP1 genes benefit more from the combination treatment compared to those receiving only PD-(L)1 inhibitors, as shown in the POSEIDON trial.
  • The loss of KEAP1 serves as a strong predictor for the success of dual ICB, as it leads to a more favorable outcome by changing the tumor's immune environment to better engage CD4 and CD8 T cells for anti-tumor activity. *
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Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels.

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  • The term 'precancer' describes an early stage of abnormal cell development that diverges from normal tissue due to specific molecular and phenotypic changes, making these cells less reliant on typical growth signals.
  • Defining precancer is complex, and while histopathologists can identify cancerous tissues through significant changes, distinguishing precancer from non-cancerous tissues is still a work in progress in both research and clinical settings.
  • The text proposes a conceptual framework to better define precancer, focusing on molecular, pathological, clinical, and epidemiological criteria to enhance understanding and potential early interventions.
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Comprehensive biomarker testing is a crucial requirement for the optimal treatment of advanced-stage non-small cell lung cancer (NSCLC), with emerging relevance in the adjuvant treatment setting. To advance its goal of ensuring optimal therapy for persons diagnosed with lung cancer, the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) held The Summit on Optimizing Lung Cancer Biomarkers in Practice in September 2020 to align its partners toward the goal of ensuring comprehensive biomarker testing for all eligible patients with NSCLC. The ACS NLCRT's Strategic Plan for Advancing Comprehensive Biomarker Testing in NSCLC, a product of the summit, comprises actions to promote comprehensive biomarker testing for all eligible patients.

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Comprehensive biomarker testing for patients with non-small cell lung cancer is critical for selecting appropriate targeted therapy or immunotherapy. Ensuring timely ordering, processing, and reporting is key to optimizing patient outcomes. However, various factors can prevent or delay patients from being offered the option of treatment selection based on comprehensive biomarker testing.

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Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT.

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Rationale Of The Trial: Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We investigated the safety and tolerability of IMA202 in a first-in-human, dose escalation basket trial in human leucocyte antigen A*02:01 positive patients with melanoma-associated antigen A1 (MAGEA1)-positive advanced solid tumors.

Trial Design: The 2+2 trial design was an algorithmic design based on a maximally acceptable dose-limiting toxicity (DLT) rate of 25% and the sample size was driven by the algorithmic design with a maximum of 16 patients.

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Background: Adenoid cystic carcinoma is a rare subtype of triple-negative breast carcinoma. These low-grade tumours, which are treated by simple mastectomy and have an excellent prognosis compared to other triple-negative breast carcinomas. Solid-variant adenoid cystic carcinomas have basaloid features and are difficult to distinguish morphologically from other triple-negative breast cancers.

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The tumor microenvironment (TME) plays a fundamental role in tumorigenesis, tumor progression, and anti-cancer immunity potential of emerging cancer therapeutics. Understanding inter-patient TME heterogeneity, however, remains a challenge to efficient drug development. This article applies recent advances in machine learning (ML) for survival analysis to a retrospective study of NSCLC patients who received definitive surgical resection and immune pathology following surgery.

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  • Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive type of lung cancer that has both normal cell and unusual cell features.
  • Researchers studied PSC samples and compared them to normal lung tissues to understand their differences better, focusing on genetics and immune responses.
  • They found 27 gene mutations in PSC, discovered two types of PSC based on immune system activity, and noted that one type (Immune High) had better survival rates, showing that the immune system plays a big role in fighting this cancer.
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  • * Findings showed a high overall objective response rate (>75%) with the use of brentuximab vedotin in conjunction with either ipilimumab or nivolumab, indicating effective treatment options for patients.
  • * Identified specific immune markers in the blood that correlate with treatment resistance, which could help in tailoring patient treatment plans for those with treatment-resistant relapsed HL.
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  • * Higher lung cancer incidence and mortality rates are observed among Black men and young women, often linked to geographic differences in screening access and socioeconomic status.
  • * Strategies to improve outcomes include modifying screening guidelines to consider demographic factors, enhancing patient and clinician education, and increasing access to biomarker testing and screening.
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The United States government makes a substantial investment in biomedical training programs each year. However, for most trainees, these opportunities do not translate into career progression in academic research pathways. Only about one-fifth of postdoctoral fellows eventually secure a tenure-track faculty position, and even among these candidates, attrition is high.

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The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of cancer patients. The development of personalized medicine represents a turning point and a new paradigm in cancer management, as biomarkers enable oncologists to tailor treatments based on the unique molecular profile of each patient's tumor. In this review, we discuss the scientific milestones of cancer biomarkers and explore future possibilities to improve the management of patients with solid tumors.

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  • Granulomatous Mycosis Fungoides (GMF) is a rare and severe type of mycosis fungoides that features a granulomatous infiltrate and generally has worse outcomes than typical mycosis fungoides.
  • The study investigated immune responses in GMF and Mycosis Fungoides with Large Cell Transformation (MFLCT) by examining various markers in skin biopsies from 49 patients.
  • Findings indicated that patients with GMF showed distinct immune profiles, including increased Tbet, RORγT, and PD-L1, while certain factors like low levels of RORγT and advanced disease stage correlated with poorer survival rates.
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Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) has a desmoplastic tumor stroma and immunosuppressive microenvironment. Galectin-3 (GAL3) is enriched in PDAC, highly expressed by cancer cells and myeloid cells. However, the functional roles of GAL3 in the PDAC microenvironment remain elusive.

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The translation elongation factor eEF1A promotes protein synthesis. Its methylation by METTL13 increases its activity, supporting tumor growth. However, in some cancers, a high abundance of eEF1A isoforms is associated with a good prognosis.

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