Aik Choon Tan

Aik Choon Tan
University of Utah | UOU

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491
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Introduction
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Publications

Publications (491)
Preprint
Background: Immune checkpoint inhibitors (ICIs) have significantly improved patient survival outcomes across various cancer types. However, their use is often associated with immune-related adverse events (irAEs), posing challenges in clinical management. Understanding the incidence, severity, and risk factors of irAEs is critical for optimizing IC...
Article
Full-text available
Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their d...
Article
364 Background: Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced cancers such as lung, bladder, head and neck, colorectal cancers, and melanoma. Psychological distress may promote pro-inflammatory states which can exacerbate immune-related adverse events (irAEs) among ICI-treated cancer patients. This study assessed the i...
Article
Combining MEK and autophagy inhibitors in preclinical PDAC mouse models resulted in tumor regressions and improved rodent survival. These findings provided the rationale for clinical investigation of this combination. The phase 1 MEKiAUTO trial evaluated combination cobimetinib, HCQ, with or without atezolizumab in 14 patients (pts) with KRAS-mutat...
Article
Background Obesity has been identified as an established risk factor in the development of clear cell renal cell carcinoma (ccRCC). ccRCC arises from the proximal convoluted tubule (PCT) of the kidney which is also the site of obesity-associated chronic kidney disease. Obesity can lead to chronic cellular insults which may lead to DNA injury and wh...
Article
Gene expression profiling technologies have revolutionized cell biology, enabling researchers to identify gene signatures linked to various biological attributes of melanomas, such as pigmentation status, differentiation state, proliferative versus invasive capacity, and disease progression. Although the discovery of gene signatures has significant...
Article
Emerging evidence supports the important role of the tumor microbiome in oncogenesis, cancer immune phenotype, cancer progression, and treatment outcomes in many malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and its potential roles in association with clinical outcomes, such as survival, in patients with meta...
Article
Full-text available
Objective Many patients with melanoma treated with immune checkpoint inhibitors (ICIs) do not derive response. Preclinical and retrospective studies identified that inhibition of the cyclooxygenase (COX) pathway may improve response to ICI treatment. Methods This prospective single site phase II trial accrued patients with advanced/metastatic mela...
Article
Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation’s ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA sequencing data from the Oncology Research Informa...
Conference Paper
Full-text available
Background: Myocarditis (MC) secondary to ICIs is a severe immune-related adverse event (irAE) and may co-occur with myositis (MYS) and myasthenia gravis (MG), presenting as the triple M overlap syndrome (TMOS). Limited data have been reported on TMOS as a fatal irAE complication. We sought to understand the clinical complexities of TMOS and applie...
Article
e14667 Background: A prominent challenge advancing immunotherapy is the heterogeneity of resistance mechanisms leading to drug development failure despite efficacy in subgroup of patients. To address these shortcomings, precision medicine platforms aimed at prospectively stratifying patients into treatment groups based on tumor mutational burden (T...
Article
11565 Background: Cytotoxic chemotherapy in patients (pts) with unresectable malignant peripheral nerve sheath tumors (MPNSTs) affords minimal benefit with significant toxicity. Pexidartinib, an inhibitor of colony-stimulating factor-1 receptor (CSF1R), targets infiltrating M2 macrophages which correlate with disease progression; combination with a...
Article
2643 Background: Myocarditis (MC) secondary to ICIs is a severe immune-related adverse event (irAE) and may co-occur with myositis (MYS) and myasthenia gravis (MG), presenting as the triple M overlap syndrome (TMOS). Limited data have been reported on TMOS as a fatal irAE complication. We sought to understand the clinical complexities of TMOS and a...
Article
e21502 Background: Adjuvant anti-PD1 is the standard of care for high-risk resectable melanoma but many still suffer recurrence. We report a single institution observational study of patients who received adjuvant anti-PD1 with a particular focus on those who recurred. Methods: Through an approved protocol by Huntsman Cancer Institute IRB, patients...
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Obesity is a highly prevalent metabolic disease and an established risk factor for colon cancer. However, critical biological pathways underpinning this relationship remain undetermined. Herein, we integrate human and murine colon tumor transcriptomic data to identify obesity-responsive pathways conserved between species. Human colon cancer samples...
Article
Despite the rise of global obesity rates and obesity’s implication in increased colon cancer risk, the understanding of mechanisms underlying these associations and opportunities for interception are limited. This work leveraged transcriptomic data from colon tumors to identify pathways and biologically relevant functions that characterize the tumo...
Article
Background: Neoantigen-based personalized cancer vaccines carry significant promise in treating solid malignancies. However, there are uncertainties regarding the choice between the primary or the metastatic tumor for neoantigen prediction in individual patients. Here, we conducted a thorough examination of somatic variations in 676 patients who ha...
Article
Background: Emerging literature has identified key immune cell populations that appear to significantly impact immune activation or suppression in patients with cancer. We investigated candidate populations and their differential infiltration within tumors as estimated from mRNA co-expression levels of corresponding cellular markers. Methods: We ut...
Article
Candida are commonly found in bile collected during surgery in pancreatic ductal adenocarcinoma (PDAC) patients. However, their significance in tumor biology and oncological outcome is unclear. PDAC patients receiving neoadjuvant therapy and pancreatectomy with intraoperative bile fungal culture were identified (N=40) in a prospective single-instit...
Article
Obesity is a well-defined risk factor for colon cancer (CC). In the current study, we investigated the paracrine influences between tumors and adjacent adipose tissue to understand the interactions between adipose-tumor using transcriptomics data. Stage I-III newly diagnosed CC patients (n = 130) as part of the ColoCare Study at the Huntsman Cancer...
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Full-text available
Super enhancers (SE), large genomic elements that activate transcription and drive cell identity, have been found with cancer-specific gene regulation in human cancers. Recent studies reported the importance of understanding the cooperation and function of SE internal components, i.e., the constituent enhancers (CE). However, there are no pan-cance...
Article
Full-text available
Purpose Immune checkpoint inhibitors (ICIs) have significantly improved the survival of patients with cancer and provided long-term durable benefit. However, ICI-treated patients develop a range of toxicities known as immune-related adverse events (irAEs), which could compromise clinical benefits from these treatments. As the incidence and spectrum...
Article
PURPOSE Recent evidence has shown that higher tumor mutational burden strongly correlates with an increased risk of immune-related adverse events (irAEs). By using an integrated multiomics approach, we further studied the association between relevant tumor immune microenvironment (TIME) features and irAEs. METHODS Leveraging the US Food and Drug A...
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Full-text available
Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10%–20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of h...
Conference Paper
Full-text available
Background Neoantigen-based personalized cancer vaccines carry significant promise in treating solid malignancies. However, there are still uncertainties regarding the choice between the primary and metastatic tumor for neoantigen prediction in individual patients. Here, we conducted a thorough examination of somatic variations in 45 patients who h...
Conference Paper
Full-text available
Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for multiple advanced solid cancers by reinvigorate patient’s own immune system to eliminate tumour cells for durable responses in selected patients. However, the benefit of ICIs is usually hampered by immune-related adverse events (irAEs), which are autoimmune reactio...
Conference Paper
Full-text available
Background The rapid advancement of immunotherapies in oncology precipitates the need for clinicogenomic databases to verify published findings and to augment related discoveries. Growing bodies of real-world data (RWD) present such opportunities. We used one RWD source, Aster Insights’ ORIEN Avatar® database, to develop criteria for estimating rea...
Article
Importance Combining immune checkpoint blockade (ICB) with chemotherapy improves outcomes in patients with metastatic gastric and gastroesophageal junction (G/GEJ) adenocarcinoma; however, whether this combination has activity in the perioperative setting remains unknown. Objective To evaluate the safety and preliminary activity of perioperative c...
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Full-text available
EWSR1 fusions are highly promiscuous and are associated with unique malignancies, clinical phenotypes, and molecular subtypes. However, rare fusion partners (RFP) of EWSR1 has not been well described. Here, we conducted a cross-sectional, retrospective study of 1,140 unique tumors harboring EWSR1 fusions. We identified 64 unique fusion partners. RF...
Preprint
Both aging spots (hyperpigmentation) and hair graying (lack of pigmentation) are associated with aging, two seemingly opposite pigmentation phenotypes. It is not clear how they are mechanistically connected. This study investigated the underlying mechanism in a family with an inherited pigmentation disorder. Clinical examinations identified acceler...
Article
Head and neck squamous cell carcinomas (HNSCC) remain a poorly understood disease clinically and immunologically. HPV is a known risk factor of HNSCC associated with better outcome, whereas HPV‐negative HNSCC are more heterogeneous in outcome. Gene expression signatures have been developed to classify HNSCC into four molecular subtypes (classical,...
Article
Estrogen receptor (ER) α expression and associated signaling is a major driver of over two-thirds of all breast cancers (BC). ER targeting strategies are typically used as a first-line therapy in patients with steroid receptor positive (SR+) disease. Secondary resistance to anti-estrogenic agents may occur with clonal expansion and disease progress...
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Full-text available
Adaptive drug resistance, OGT, cancer cell reprogramming, epigenetics, metabolism, drug tolerant persisters
Preprint
Full-text available
Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation’s ability to kill cells. We investigated whether some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. We examined the RNA-seq data from the Oncology Research Information Exchange N...
Article
Full-text available
Aims: Drivers of the drug tolerant proliferative persister (DTPP) state have not been well investigated. Histone H3 lysine-4 trimethylation (H3K4me3), an active histone mark, might enable slow cycling drug tolerant persisters (DTP) to regain proliferative capacity. This study aimed to determine H3K4me3 transcriptionally active sites identifying a...
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Full-text available
Patients with human papillomavirus-negative head and neck squamous cell carcinoma (HPV-negative HNSCC) have worse outcomes than HPV-positive HNSCC. In our study, we used a published dataset and investigated the microbes enriched in molecularly classified tumor groups. We showed that microbial signatures could distinguish Hypoxia/Immune phenotypes s...
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Full-text available
Background: Pembrolizumab is FDA approved for tumors with tumor mutational burden (TMB) of ≥10 mutations/megabase (mut/Mb). However, the response to immune checkpoint inhibitors (ICI) varies significantly among cancer histologies. We describe the landscape of frameshift mutations (FSs) and evaluated their role as a predictive biomarker to ICI in a...
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Full-text available
Preclinical genetically engineered mouse models (GEMMs) of lung adenocarcinoma are invaluable for investigating molecular drivers of tumor formation, progression, and therapeutic resistance. However, histological analysis of these GEMMs requires significant time and training to ensure accuracy and consistency. To achieve a more objective and standa...
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Full-text available
Pathway-level survival analysis offers the opportunity to examine molecular pathways and immune signatures that influence patient outcomes. However, available survival analysis algorithms are limited in pathway-level function and lack a streamlined analytical process. Here we present a comprehensive pathway-level survival analysis suite, PATH-SURVE...
Article
3126 Background: Neoantigen-based personalized cancer vaccines carry significant promise in treating solid malignancies. For the purpose of neoantigen prediction, questions remain on the suitability of the primary versus the metastatic tumor of an individual patient (pt). Here we performed an in-depth analysis of somatic variants of 45 pts with pai...
Article
9557 Background: Despite advancements in checkpoint inhibitor-based immunotherapy (IO), patients (pts) with advanced melanoma who have progressed on Ipi + nivolumab (Nivo) continue to have poor prognosis. Several studies support a dose-response activity of Ipi. One promising combination for these pts is Ipi 10mg/kg (Ipi10) + TMZ. TMZ depletes regul...
Article
6053 Background: High TMB is associated with immune checkpoint inhibitor (ICI) response in many solid tumors. However, obtaining sufficient tumor specimens for testing in a routine clinical setting could be a challenge. We evaluated TMB from whole-exome sequencing (WES) of cfDNA as a surrogate for tDNA TMB in R/M HNSCC pts treated with C+N. Methods...
Preprint
Full-text available
Background: Despite advancements in checkpoint inhibitor-based immunotherapy, patients with advanced melanoma who have progressed on standard dose ipilimumab (Ipi) + nivolumab continue to have poor prognosis. Several studies support a dose-response activity of Ipi, and one promising combination is Ipi 10mg/kg (Ipi10) + temozolomide (TMZ). Methods:...
Preprint
Full-text available
Emerging evidence supports the important role of the tumor microbiome in oncogenesis, cancer immune phenotype, cancer progression, and treatment outcomes in many malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and potential roles in association with clinical outcomes, such as survival, in patients with metastat...
Preprint
Full-text available
Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10–20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of ho...
Article
Full-text available
Head and neck squamous cell carcinoma (HNSCC) has one of the most hypoxic and immunosuppressive tumor microenvironments (TME) among solid tumors. However, there is no proven therapeutic strategy to remodel the TME to be less hypoxic and proinflammatory. In this study, we classified tumors according to a Hypoxia-Immune signature, characterized the i...
Article
Full-text available
It has been challenging to target mutant KRAS (mKRAS) in colorectal cancer (CRC) and other malignancies. Recent efforts have focused on developing inhibitors blocking molecules essential for KRAS activity. In this regard, SOS1 inhibition has arisen as an attractive approach for mKRAS CRC given its essential role as a guanine nucleotide exchange fac...
Article
Hematoxylin and eosin (H&E) staining is the most common type of histopathological images used for quantitative data analysis. For histopathological image analysis, nucleus segmentation represents one of the initial steps in quantitative data analysis pipelines. Recently, deep learning methods for nucleus segmentation on histopathological images bec...
Article
Advances in immunotherapy including immune checkpoint inhibitors (ICIs) have transformed the standard of care of many cancers including melanoma. However, the benefit of ICIs is hampered by immune related adverse events (irAEs). The frequency of irAEs varies between ICI treatments and cancer types. These irAEs represent autoimmune reactions that ca...
Article
The tumor microbiome has recently been shown to play a key role in the context of oncogenesis, cancer immune phenotype, cancer progression and treatment outcomes in a variety of cancers. We investigated the possible associations between tumor microbiome and successful treatment outcomes with immune checkpoint blockade (ICB) in patients with metasta...
Article
Immune checkpoint inhibitors (ICI) have provided durable responses in a subset of patients in multiple solid tumor types. However, developing robust and reproducible predictive gene signatures for ICIs remains a challenge partly due to the lack of systematic comparisons across a large pan-cancer transcriptomics compendia. We recently developed Immu...
Article
A tumor microbiome has recently been established as present in many cancer types. Further study is needed to define the scope of its role in cancer tumorigenesis, progression, and treatment outcomes. The Oncology Research Information Exchange Network (ORIEN) established a collaboration among eight member institutions to study the tumor microbiome a...
Article
Full-text available
Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors, have immunomodulatory properties and have offered promising results when combined with anti-PD-1 agents. We conducted...
Preprint
Full-text available
Pathway-level survival analysis offers the opportunity to examine molecular pathways and immune signatures that influence patient outcomes. However, available survival analysis algorithms are limited in pathway-level function and lack a streamlined analytical process. Here we present a comprehensive pathway-level survival analysis suite, DRPPM-PATH...
Article
Full-text available
Multiple Myeloma (MM) is an incurable plasma cell malignancy often treated by autologous stem cell transplant (ASCT). Clinical response to ASCT has been associated with DNA repair efficiency. Here we interrogated the role of the base excision DNA repair (BER) pathway in MM response to ASCT. Across 450 clinical samples and six disease stages, expres...
Article
Nucleus segmentation represents the initial step for histopathological image analysis pipelines, and it remains a challenge in many quantitative analysis methods in terms of accuracy and speed. Recently, deep learning nucleus segmentation methods have demonstrated to outperform previous intensity- or pattern-based methods. However, the heavy comput...
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Full-text available
Patients with advanced thyroid cancer, including advanced papillary thyroid cancer and anaplastic thyroid cancer (ATC), have low survival rates because of the lack of efficient therapies available that can combat their aggressiveness. A total of 90% of thyroid cancers have identifiable driver mutations, which often are components of the MAPK pathwa...
Article
Direct blockade of KRAS driver mutations in colorectal cancer (CRC) has been challenging. Targeting SOS1, a guanine nucleotide exchange factor, has arisen as an attractive approach for KRAS-mutant CRC. Here, we describe the development of novel SOS1 degraders and their activity in patient-derived CRC organoids (PDO). The design of these degraders a...
Conference Paper
Background Immune checkpoint inhibitors (ICIs) have made significant improvements in the treatment of cancer patients (pts), but many continue to experience primary or secondary resistance. Here, we leveraged clinical and genomic data to identify prognostic biomarkers in pts treated with ICIs utilizing a pan-cancer approach. Methods Patients were...
Conference Paper
Background Evidence supports the association between tumor-infiltrating lymphocytes with disease prognosis and response to immunotherapy. Here, we evaluated the prognostic value of an immunoscore reflecting CD3+ and CD8+ T cell density in patients with advanced malignancies treated with immune checkpoint inhibitors (ICIs). Methods We utilized real...
Conference Paper
Background PD1 immune checkpoint inhibitors (ICIs) have resulted in significant improvements in the care of patients with advanced malignancies. PD1 based combinations including with CTLA4 and LAG3 represent the future of ICI immunotherapy and there is a need to better understand the rationale for investigating combinations involving other immune m...
Conference Paper
Background Emerging evidence supports an important role for the tumor microbiome in relation to oncogenesis, cancer immune phenotype, cancer progression and treatment outcomes in a number of malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and potential roles in association with clinical outcomes, such as surviv...
Preprint
Full-text available
Background It has been challenging to develop agents directly targeting KRAS driver mutations in colorectal cancer (CRC). Recent efforts have focused on developing inhibitors targeting SOS1 as an attractive approach for KRAS -mutant cancers. Here, we aimed to study the translational role of SOS1 in CRC using patient-derived organoids (PDOs). Metho...
Article
Alveolar macrophages (AMs) are tissue-resident cells of the lower airways that perform many homeostatic functions critical for pulmonary health and protection against pathogens. However, little is known about the factors that shape AMs during healthy aging. In these studies, we sought to characterize age-related changes in AM phenotype, function, a...
Article
Full-text available
Although substantial progress has been made in treating patients with advanced melanoma with targeted and immuno-therapies, de novo and acquired resistance is commonplace. After treatment failure, therapeutic options are very limited and novel strategies are urgently needed. Combination therapies are often more effective than single agents and are...
Article
Advances in immunotherapy, including immune checkpoint inhibitors (ICIs), have transformed the standard of care for many types of cancer including melanoma. ICIs have improved the overall outcome of melanoma patients; however, a significant proportion of patients suffer from primary or secondary tumor resistance. Therefore, there is an urgent need...
Article
Introduction: Pancreatic cystic lesions (PCL) are common and a subset of mucinous cysts will transform into pancreatic ductal adenocarcinoma (PDAC). However, predicting which of these mucinous PCL may progress to PDAC and warrant surgery remains a clinical challenge. Moreover, identifying those clinically emergent mucinous PCL for which a surveilla...
Article
Full-text available
Background We hypothesized that a gender difference in clinical response may exist to adjuvant CTLA4 blockade with ipilimumab versus high-dose IFNα (HDI). We investigated differences in candidate immune biomarkers in the circulation and tumor microenvironment (TME). Patients and methods This gender-based analysis was nested within the E1609 trial...
Article
2618 Background: Despite the significant improvements in treating cancer with immune checkpoint inhibitors (ICIs), many patients (pts) do not achieve disease control. Using Oncology Research Information Exchange Network (ORIEN) Avatar real-world data conducted under the Total Cancer Care protocol we investigate predictive biomarkers of ICI benefits...
Article
2619 Background: Immune checkpoint inhibitors (ICIs) have made significant improvements in the treatment of cancer patients (pts), but many continue to experience primary or secondary resistance. Here, we leveraged clinical and genomic data to identify prognostic biomarkers in pts treated with ICIs utilizing a pan-cancer approach. Methods: Pts were...
Article
Full-text available
Super enhancers (SEs) are broad enhancer domains usually containing multiple constituent enhancers that hold elevated activities in gene regulation. Disruption in one or more constituent enhancers causes aberrant SE activities that lead to gene dysregulation in diseases. To quantify SE aberrations, differential analysis is performed to compare SE a...
Article
The cover image is based on the Research Article Neoadjuvant endocrine therapy expands stromal populations that predict poor prognosis in estrogen receptor‐positive breast cancer by Heather M. Brechbuhl et al., https://doi.org/10.1002/mc.23377.
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Full-text available
High-throughput transcriptomic and proteomic analyses are now routinely applied to study cancer biology. However, complex omics integration remains challenging and often time-consuming. Here, we developed DRPPM-EASY, an R Shiny framework for integrative multi-omics analysis. We applied our application to analyze RNA-seq data generated from a USP7 k...
Article
Full-text available
Distinct lung stem cells give rise to lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). ΔNp63, the p53 family member and p63 isoform, guides the maturation of these stem cells through the regulation of their self-renewal and terminal differentiation; however, the underlying mechanistic role regulated by ∆Np63 in lung cancer development...