Aik Choon Tan

Aik Choon Tan
Moffitt Cancer Center

About

418
Publications
48,836
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
11,852
Citations
Introduction
Skills and Expertise

Publications

Publications (418)
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
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.
Article
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...
Article
Full-text available
Background Melanoma of unknown primary (MUP) represents a poorly understood group of patients both clinically and immunologically. We investigated differences in prognosis and candidate immune biomarkers in patients with unknown compared with those with known primary melanoma enrolled in the E1609 adjuvant trial that tested ipilimumab at 3 and 10 m...
Article
Full-text available
Effective treatment options for head and neck squamous cell carcinoma (HNSCC) are currently lacking. We exploited the drug response and genomic data of the 28 HNSCC cell lines, screened with 4,518 compounds, from the PRISM repurposing dataset to uncover repurposing drug candidates for HNSCC. A total of 886 active compounds, comprising of 418 target...
Article
The tumor microenvironment (TME) is an important modulator of response and resistance to endocrine therapy in estrogen receptor alpha (ER) positive breast cancer. Endocrine therapy is highly effective at reducing tumor burden and preventing recurrence in most estrogen receptor alpha (ER) positive breast cancers. Existing drugs work either directly...
Article
Full-text available
Tyrosine kinase inhibitors (TKIs) targeting EGFR-mutant lung cancers promote a range of tumor regression responses to yield variable residual disease, a likely incubator for acquired resistance. Herein, rapid transcriptional responses induced by TKIs early in treatment that associate with the range of patient responses were explored. RNAseq was per...
Article
Full-text available
Background Sex differences in tumor immunity and response to immunotherapy were shown in murine models and descriptive analyses from recent clinical trials. We recently reported that female gender is a favorable prognostic marker for survival benefit following ipilimumab and high dose interferon-alfa (HDI) adjuvant therapy of high-risk melanoma in...
Article
Full-text available
Background We recently reported data supporting the unknown primary status as a potentially distinct prognostic group among high-risk melanoma patients treated with ipilimumab and high dose interferon-alfa (HDI) in the ECOG-ACRIN E1609 trial (N=1670) with improved RFS and OS outcomes compared to known primary. Therefore, we investigated differences...
Poster
Preclinical mouse models of lung adenocarcinoma (LUAD) are invaluable for the discovery of molecular drivers of tumor formation, progression, and therapeutic resistance. Histological analyses of preclinical models require significant training to ensure accuracy and consistency. Clinical pathologists provide the gold standard in this approach, but r...
Preprint
Full-text available
Super enhancers (SEs) are broad enhancer domains usually containing multiple constitute enhancers with significantly elevated activities. The constitute enhancers work together through chromatin looping to build up distinct regulatory properties of SEs. Aberrant SE activities, which are critical to understand disease mechanisms, could be raised by...
Article
Full-text available
A continuing challenge in modern medicine is the identification of safer and more efficacious drugs. Precision therapeutics, which have one molecular target, have been long promised to be safer and more effective than traditional therapies. This approach has proven to be challenging for multiple reasons including lack of efficacy, rapidly acquired...
Article
Full-text available
The tumor immune microenvironment (TIME) encompasses many heterogeneous cell types that engage in extensive crosstalk among the cancer, immune, and stromal components. The spatial organization of these different cell types in TIME could be used as biomarkers for predicting drug responses, prognosis and metastasis. Recently, deep learning approaches...
Article
Full-text available
There is a clear need to identify targetable drivers of resistance and potential biomarkers for salvage therapy for melanoma patients refractory to the combination of BRAF and MEK inhibition. In the present study, we performed whole exome sequencing on BRAF-V600E mutant melanoma patient tumors refractory to the combination of BRAF/MEK inhibition an...
Poster
Analysis by a clinical pathologist is the gold standard for preclinical histological analysis but may be difficult to obtain due to the cost and availability of their services. As an alternative we have developed a digital pathology pipeline to segment, grade, and analyze lung adenocarcinoma tumors. This convolutional neural network (CNN) was train...
Article
PURPOSE The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care ha...
Article
The heterogeneous cell types of the tumor-immune microenvironment (TIME) play key roles in determining cancer progression, metastasis, and response to treatment. We report the development of TIMEx, a novel tumor-immune microenvironment deconvolution method emphasizing on estimating infiltrating immune cells for bulk transcriptomics using pan-cancer...
Article
Rearranged during transfection (RET) rearrangements occur in 1% to 2% of lung adenocarcinomas as well as other malignancies and are now established targets for tyrosine kinase inhibitors. We developed three novel RET fusion-positive (RET+) patient-derived cancer cell lines, CUTO22 [kinesin 5B (KIF5B)-RET fusion], CUTO32 (KIF5B-RET fusion), and CUTO...
Article
Full-text available
Significance The nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NLRP3) inflammasome, an intracellular complex that regulates maturation and release of interleukin (IL)-1β, is active in biopsies of metastatic melanoma. Here, we demonstrate that NLRP3 activation in melanoma cells drives tumor progression in mice...
Article
Full-text available
The initiation and progression of cancers reflect the underlying process of somatic evolution, in which the diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack...
Article
Preclinical mouse models of lung adenocarcinoma are invaluable for the discovery of molecular drivers of tumor formation, progression, and therapeutic resistance. Histological analyses of these preclinical models require significant investments of time and training to ensure accuracy and consistency. Analysis by a clinical pathologist is the gold s...
Preprint
Full-text available
A continuing challenge in modern medicine is the identification of safer and more efficacious drugs. Precision therapeutics, which have one molecular target, have been long promised to be safer and more effective than traditional therapies. This approach has proven to be challenging for multiple reasons including lack of efficacy, rapidly acquired...
Article
The cover image is based on the Research Article Effects of checkpoint kinase 1 inhibition by prexasertib on the tumor immune microenvironment of head and neck squamous cell carcinoma by Ritu Chaudhary et al.,https://doi.org/10.1002/mc.23275.
Conference Paper
Preclinical mouse models of lung adenocarcinoma are invaluable for the discovery of molecular drivers of tumor formation, progression, and therapeutic resistance. Histological analyses of these preclinical models require significant investments of time and training to ensure accuracy and consistency. Analysis by a clinical pathologist is the gold s...
Article
Prognosis for patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) remains poor. Development of more effective and less toxic targeted therapies is necessary for HNSCC patients. Checkpoint kinase 1 (CHK1) plays a vital role in cell cycle regulation and is a promising therapeutic target in HNSCC. Prexasertib, a CHK...
Article
Two factors known to contribute to the development of myelodysplastic syndrome (MDS) and other blood cancers are (i) somatically acquired mutations in components of the spliceosome and (ii) increased inflammation. Spliceosome genes, including SF3B1, are mutated at high frequency in MDS and other blood cancers; these mutations are thought to be neom...
Article
Full-text available
Background Metastasis is the primary cause of cancer mortality accounting for 90% of cancer deaths. Our understanding of the molecular mechanisms driving metastasis is rudimentary. Results We perform whole exome sequencing (WES), RNA sequencing, methylation microarray, and immunohistochemistry (IHC) on 8 pairs of non-small cell lung cancer (NSCLC)...
Conference Paper
P53 is frequently mutated in a wide variety of tumors; yet, the regulation and expression of downstream targets during tumor progression and response to therapy is unknown. Here, we use Kras/p53-driven lung adenocarcinoma in the mouse as a model system to identify p53-driven molecular signatures that predict lung adenocarcinoma progression. Using t...
Article
Resistance to immunotherapy is a significant challenge, and the scarcity of human models hinders the identification of the underlying mechanisms. To address this limitation, we constructed an autologous humanized mouse (aHM) model with hematopoietic stem and progenitor cells (HSPCs) and tumors from two melanoma patients progressing to immunotherapy...
Article
Purpose: Thyroid disease is a frequent comorbidity in women with breast cancer (BC), and many require thyroid hormone(TH) replacement therapy(THRT). We postulated that THRT has a deleterious clinical effect mechanistically through hormonal interactions, nuclear receptor cross-talk and upregulation of high-risk BC genes. Experimental design: Obse...
Article
Small cell lung cancer (SCLC) can be sub-grouped into common 'pure' and rare 'combined' SCLC (c-SCLC). c-SCLC features a mixed tumor histology of both SCLC and non-small cell lung cancer (NSCLC). We performed targeted exon sequencing on 90 SCLC patients, including two with c-SCLC, and discovered RUNX1T1 amplification specific to small cell tumors o...
Article
Full-text available
New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identi...
Article
Full-text available
New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identi...
Article
Full-text available
New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identi...
Conference Paper
Covalent inhibitors of KRASG12C mutants allow specific targeting of KRAS driven signaling yet early studies suggest bypass signaling as a mechanism of resistance. Understanding adaptive signaling mechanisms enabling cells to survive KRASG12C inhibition could identify combination therapies and associated predictive biomarkers. We employed KRASG12C m...
Article
Full-text available
Immunotherapy, such as anti-PD1, has improved the survival of patients with metastatic melanoma. However, predicting which patients will respond to immunotherapy remains a significant knowledge gap. In this study we analyzed pre-immunotherapy treated tumors from 52 patients with metastatic melanoma and monitored their response based on RECIST 1.1 c...
Article
Melanoma is an aggressive, deadly skin cancer derived from melanocytes, a neural crest cell derivative. Melanoma cells mirror the developmental program of neural crest cells in that they exhibit the same gene expression patterns and utilize similar cellular mechanisms, including increased cell proliferation, epithelial‐mesenchymal transition, and m...
Article
Full-text available
Melanoma represents the most serious type of skin cancer. Although recent years have seen advances using targeted and immunotherapies, most patients remain at high risk for tumor recurrence. Here we show that IRAK-M, a negative regulator of MyD88 signaling, is deficient or low in melanoma and expression levels correlate with patient survival. Induc...
Article
Full-text available
Since the discovery of CHD1L in 2008 it has emerged as an oncogene implicated in the pathology and poor prognosis of a variety of cancers, including gastrointestinal cancers. However, a mechanistic understanding of CHD1L as a driver of colorectal cancer (CRC) has been limited. Until now, there have been no reported inhibitors of CHD1L, also limitin...
Article
Full-text available
Current treatment for patients with metastatic melanoma include molecular-targeted therapies and immune checkpoint inhibitors. However, a subset of melanomas are difficult-to-treat. These melanomas include those without the genetic markers for targeted therapy, non-responsive to immunotherapy, and those who have relapsed or exhausted their therapeu...
Article
Small cell lung cancer (SCLC) represents ∼15% of all lung cancer diagnoses in the US and has a particularly poor prognosis. We hypothesized that kinases regulating SCLC survival pathways represent therapeutically targetable vulnerabilities whose inhibition may improve SCLC outcome. A shRNA library targeting all human kinases was introduced into sev...
Article
e18541 Background: Despite considerable advancements in the standard therapies including surgery, chemotherapy and radiotherapy, the clinical outcome for head and neck squamous cell carcinoma (HNSCC) remains poor due to tumor recurrence and metastasis. Molecular-targeted therapies have evolved as novel and promising treatment for HNSCC patients. He...
Article
Purpose: The purpose of this study was to evaluate the rational combination of TORC 1/2 inhibitor TAK-228 and Aurora A kinase inhibitor alisertib in preclinical models of triple-negative breast cancer (TNBC), and to conduct a phase 1 dose escalation trial in patients with advanced solid tumors. Rxperimental Design: TNBC cell lines and patient deri...
Article
Full-text available
Despite high initial efficacy, targeted therapies eventually fail in advanced cancers, as tumors develop resistance and relapse. In contrast to the substantial body of research on the molecular mechanisms of resistance, understanding of how resistance evolves remains limited. Using an experimental model of ALK positive NSCLC, we explored the evolut...
Article
Full-text available
Adrenocortical carcinoma (ACC) is an uncommon endocrine malignancy with limited treatment options. While the overall 5-year survival rate in patients with ACC is 35%, the disease is often rapidly progressive with long-term survival in only 5% of patients. Although tumor stage, grade, and excess hormonal activity predict unfavorable prognosis, addit...
Article
Cancer stem cells (CSC) drive growth, therapy resistance, and recurrence in head and neck squamous cell carcinoma (HNSCC). Regulation of protein translation is crucial for normal stem cells and CSCs; its inhibition could disrupt stemness properties, but translation inhibitors are limited clinically due to toxicity. SVC112 is a synthetic derivative...
Preprint
Full-text available
Melanoma is an aggressive and deadly skin cancer that develops from melanocytes, a neural crest cell derivative. Melanoma cells and neural crest cells share similar gene expression, behaviors, and cellular mechanisms. Using cross-species oncogenomics, we identified genes recurrently deleted in both human and zebrafish melanomas, which includes PRDM...
Article
Purpose: Patients with head and neck squamous cell carcinoma (HNSCC) who actively smoke during treatment have worse survival compared to never-smokers and former-smokers. We hypothesize the poor prognosis in tobacco smokers with HNSCC is, at least in part, due to ongoing suppression of immune response. We characterized the tumor immune microenviro...
Conference Paper
A majority of cutaneous melanomas harboring oncogenic driver BRAF-V600E gene mutations initially demonstrate superior responses to targeted therapy with BRAF inhibitors (BRAFi), MEK inhibitors (MEKi), or the combination of both. Unfortunately, tumor regrowth and acquired resistance to BRAF and MEK inhibitors is inevitable, and new therapies are req...
Article
Full-text available
Introduction: Tyrosine kinases are key mediators of intracellular signalling cascades and aberrations in these proteins have been implicated in driving oncogenesis through the dysregulation of fundamental cellular processes including proliferation, migration, and apoptosis. As such, targeting these proteins with small molecule tyrosine kinase inhib...
Article
Full-text available
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translate...
Article
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translate...
Article
Mucosal melanoma is a rare and aggressive subtype of melanoma that has a less favorable prognosis due to the lack of understanding and identification of oncogenic drivers. Recently, whole genome and whole exome sequencing have unveiled the molecular landscape and potential oncogenic drivers of mucosal melanoma, which remains distinct from cutaneous...
Article
The inhibitory epidermal growth factor receptor (EGFR) antibody, cetuximab, is an approved therapy for head and neck squamous cell carcinoma (HNSCC). Despite tumor response observed in some HNSCC patients, cetuximab alone or combined with radio- or chemotherapy fails to yield long-term control or cures. We hypothesize that a flexible receptor tyros...
Article
The transcatheter aortic valve replacement (TAVR) procedure has emerged as a minimally invasive treatment for patients with aortic valve stenosis (AVS). However, alterations in serum factor composition and biological activity after TAVR remain unknown. Here, we quantified the systemic inflammatory effects of the TAVR procedure and hypothesized that...