Milan Radovich's research while affiliated with Caris Life Sciences and other places
What is this page?
This page lists the scientific contributions of an author, who either does not have a ResearchGate profile, or has not yet added these contributions to their profile.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
Publications (235)
1114
Background: While estrogen receptor (ER) is well-studied in breast cancer (BC), the role of androgen receptor (AR) in prognosis and therapy response is less understood. Here, we aimed to characterize the clinicopathologic and molecular features of AR gene expression in BC subtypes. Methods: 10,728 BC samples were tested by NGS (592, NextSeq; W...
B7-H3 (CD276) is a transmembrane glycoprotein of the B7 immune checkpoint superfamily that has emerged as a promising therapeutic target. To better understand the applicability of B7-H3–directed therapies, we analyzed 156,791 samples comprising 50 cancer types to interrogate the clinical, genomic, transcriptomic, and immunologic correlates of B7-H3...
Background: Metaplastic Breast Cancer (MBC) is rare (0.2-5%), aggressive form of BC characterized by chemotherapy resistance and has worse outcomes in comparison to other BC subtypes. Resistance to chemotherapeutic agents is related to defects in intact intrinsic apoptosis pathway and the BCL2 family of proteins are the central regulators of this p...
Prostate cancer is the second leading cause of cancer-related deaths in American men. While prostate cancer patients typically respond to androgen-deprivation therapy, androgen receptor signaling inhibitor (ARSI), and/or taxane chemotherapy, patients inevitably develop resistance, and the disease progresses to an untreatable and lethal form known a...
Effective clinical management of cancer patients requires an accurate and early diagnosis, highly sensitive monitoring of minimal residual disease (MRD), and precise therapy selection. There are multiple tests available that attempt to address each of these needs independently with varying degrees of clinical utility. Caris Assure is a proprietary...
Background
Natural killer (NK) cells are non-antigen specific innate immune cells that can be redirected to targets of interest using multiple strategies, although none are currently FDA-approved. We sought to evaluate NK cell infiltration into tumors to develop an improved understanding of which histologies may be most amenable to NK cell-based th...
211
Background: The Proviral Integration site for Moloney murine leukemia virus ( PIM1, 2, and 3) kinases are frequently overexpressed in prostate cancer (PC) and associated with aggressiveness and immune evasion. PIM overexpression increases macrophage infiltration and survival in in vivo models of PC. Here, we characterized the association of PIM...
9038
Background: In NSCLC, different KRAS mutations (mt) define unique subgroups and certain co-mutations (co-mt) could have prognostic and therapeutic implications. Retrospective studies associate poor prognosis with co-mts in STK11 and KEAP1 with KRAS. It is unclear if PD-L1 expression and co-mt in KRAS mt NSCLC impacts outcomes. Methods: Molecul...
1035
Background: The androgen receptor ( AR) is a hormone-regulated transcription factor that plays an important role in breast cancer (BC) pathogenesis. While estrogen receptor inhibitors are well-studied in BC, the role of AR on prognosis and therapy is less well-known. Here we aim to characterize the clinicopathologic and molecular features of A...
e15088
Background: LY3214996 (L) is a potent inhibitor of ERK1/2 kinases that can potentially obviate resistance mechanisms in cancers that harbor BRAF, RAS, NF1, MAP2K1/2, and other MAPK alterations. Abemaciclib (A) is a CDK 4/6 inhibitor. Studies have shown that concomitant inhibition of the MAPK pathway exemplified by ERK inhibitors may augment...
e15085
Background: Cancer genome screening is becoming standard clinical practice, but the number of actionable mutations detected is limited. To expand on our previous report of the possibility that ARAF S214C and CRAF S257L located in the conserved region 2 (CR2) were actionable driver mutations, we investigated responses to targeted therapies in...
8598
Background: Thymic epithelial tumors (TETs) are rare and tend to have an indolent disease course. Follow-up consists of physical examinations and routine imaging (CT scans) with no currently available biomarkers to complement surveillance. This study aimed to assess the utility of ctDNA in MRD detection and disease monitoring in TETs. Methods:...
6589
Background: Many tissue-agnostic (TA) approvals were based on clinical trials with limited patient numbers without covering all tissue types (TT), raising the question of whether these indications were truly tissue agnostic. Real world evidence (RWE) offers an opportunity to investigate TTs not included in clinical trials/studies to answer thi...
3128
Background: Regulator of Chromosome Condensation 1 (RCC1) is the only identified guanine nucleotide exchange factor for the Ras-related nuclear protein Ran and it functions in nuclear transport, cell cycle and DNA damage response. Overexpressed in several cancer types, RCC1 is associated with poor outcomes. We aim to investigate the role of ab...
e15049
Background: Liquid biopsies have become integral to the management of patients with advanced malignancies, however significant deficiencies exist in currently used platforms. Liquid biopsy data often show unacceptably high discordance compared to gold standard tissue-based data; this is often due to false positives (FP) resulting from clonal...
3133
Background: LILRB2 is primarily expressed on myeloid cells and provides negative feedback during inflammatory response. A blocking antibody targeting LILRB2 in myeloid cells is in clinical trials. Various solid tumors are also enriched with these receptors. Here we investigate differences between LILRB2 expression in the local versus metastati...
2613
Background: The cell-surface transferrin receptor, TFR1, encoded by TFRC, imports iron-bound transferrin into cells to drive tumor proliferation. We have found worse prognosis with high TFRC expression across multiple tumor types. The mechanism by which TFRC drives tumor cell- intrinsic oncogenesis is multifactorial, but its interaction with t...
2563
Background: NK cells are part of the innate immune system that are not antigen-specific, but can be redirected to targets of interest using multiple strategies. Advantages of NK cells over T cells include the use of allogeneic off-the-shelf products and lower risk of cytokine release syndrome. Numerous NK-specific immunotherapies are under dev...
e17080
Background: The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases, a family of pro-survival kinases ( PIM1, PIM2, and PIM3), are frequently overexpressed in prostate cancer (PC) and associated with PC aggressiveness and immune evasion. Preclinical data indicate that PIM1 overexpression increases macrophage infiltratio...
2624
Background: B7-H3 ( CD276) is a transmembrane glycoprotein of the B7 superfamily that includes PD-L1 and CTLA-4. B7-H3 targeted therapeutics have demonstrated promising results in both solid tumors and hematologic cancers. To understand the applicability of B7-H3 targeted therapies, we characterized the landscape of clinical outcomes, genomic,...
9027
Background: Retrospective data suggest that SGLT2 inhibitors, commonly used in diabetes, are associated with a lower incidence of cancer development and in vivo data indicate SGLT2 plays a role in the development of NSCLC. We investigated the genomic and immunological landscape of NSCLC [adenocarcinoma (AC) or squamous cell carcinoma (SCC) his...
Background: Although there is increased awareness leading to early detection and prevention, Hispanic American (HA) men with prostate cancer (PC) continue to have greater mortality rates compared to their Non-Hispanic White (NHW) counterparts. Moreover, HA men with PC are more likely to have more advanced disease compared to NHW men. Here, we chara...
Background:
Despite favorable clinical outcomes, a subset of patients with thymic epithelial tumors (TETs) develop metastasis. The Cancer Genome Atlas (TCGA) provides genomic data on primary TETs (pTETs). This study assessed the molecular alterations and uncovered targetable pathways in metastatic TETs (mTETs).
Methods:
From 2015 to 2020, 49 pat...
Introduction
Drug-induced prolongation of the heart rate-corrected QT interval (QTc) is associated with increased risk for the potentially fatal arrhythmia torsades de pointes. Due to arrhythmia risk, clinical trials with cancer therapeutics often exclude patients based on thresholds for QTc prolongation. Our objective was to assess associations be...
Purpose
To investigate the efficacy and safety of buparlisib, an oral pan-PI3K inhibitor, in relapsed or refractory thymomas.
Methods
This was a single center, single arm, open label phase II trial of buparlisib in patients with recurrent thymoma who have progressed after at least one prior line of treatment. The primary endpoint was objective res...
Following publication of the original article [1], the authors noticed an error in Additional file 1. The incorrect Figure S5 was published. The corrected Additional file 1 is published in the correction and the original article [1] has been updated.
1041
Background: Amplification or overexpression of human epidermal growth factor receptor 2 (HER2) oncogene is present in about 15-20% of breast cancers & is a prognostic & predictive biomarker. Additional ERBB2/HER2 alterations have become apparent on tumor next generation sequencing (NGS), including activating kinase domain mutations & fusions....
e20623
Background: Thymomas are rare neoplasms in the anterior mediastinum that account for less than 1% of tumors. The presence of immune cells within the tumor is one of the cardinal features of thymomas. However, the nature of the immune infiltration is not well characterized. Methods: Deconvolution of the gene expression of thymomas in the TCGA...
Purpose:
The PI3K pathway is dysregulated in the majority of triple-negative breast cancer(TNBCs), yet single agent inhibition of PI3K has been ineffective in TNBC. PI3K inhibition leads to an immediate compensatory up-regulation of the Wnt pathway. Dual targeting of both pathways is highly synergistic against TNBC models in vitro and in vivo. We...
Background
Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific t...
Germline whole exome sequencing from molecular tumor boards has the potential to be repurposed to support clinical pharmacogenomics. However, accurately calling pharmacogenomics-relevant genotypes from exome sequencing data remains challenging. Accordingly, this study assessed the analytical validity of the computational tool, Aldy, in calling phar...
Purpose: Patients with triple negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase 2, multicenter trial that randomized TNBC p...
Introduction: Triple-negative breast cancer (TNBC) is a devastating disease accompanied with substantial morbidity and mortality with very few tools in the clinical armamentarium to improve outcomes. The PI3K pathway is activated in the majority of TNBCs. However, single-agent inhibition of PI3K has seen limited clinical efficacy. We have previousl...
BACKGROUND: The anti‐cancer efficacy of sunitinib and axitinib are in part mediated through inhibition of tumor‐expressed vascular endothelial growth factor receptors (VEGFRs). In cardiomyocytes, VEGFR signaling is known to be cardio‐protective. As a result, sunitinib, and axitinib can cause cardiomyopathy in up to 30% of patients, which manifests...
PURPOSE
Precision medicine approaches, including germline pharmacogenetics (PGx) and management of drug-drug interactions (DDIs), are likely to benefit patients with advanced cancer who are frequently prescribed multiple concomitant medications to treat cancer and associated conditions. Our objective was to assess the potential opportunities for PG...
Docetaxel therapy occasionally causes severe and life-threatening toxicities. Some docetaxel toxicities are related to exposure, and inter-individual variability in exposure has been described based on genetic variation and drug-drug interactions that impact docetaxel clearance. Cytochrome P450 3A4 (CYP3A4) and CYP3A5 metabolize docetaxel into inac...
PURPOSE
Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocate...
Background/Objective: Antibody drug conjugates (ADCs) deliver potent cytotoxic therapy in a highly targeted manner by binding cancer-specific cell surface antigens. HER2 is a receptor tyrosine kinase that is commonly amplified in breast and gastric cancers, but more recently has been shown to harbor gain-of-function activating mutations in several...
Prediction of cancer-specific drug responses as well as identification of the corresponding drug-sensitive genes and pathways remains a major biological and clinical challenge. Deep learning models hold immense promise for better drug response predictions, but most of them cannot provide biological and clinical interpretability. Visible neural netw...
Background
Most patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients.
Methods
W...
PURPOSE: Precision medicine approaches, including germline pharmacogenetics (PGx) and management of drug-drug interactions (DDIs), are likely to benefit advanced cancer patients who are frequently prescribed multiple concomitant medications to treat cancer and associated conditions. Our objective was to assess the potential opportunities for PGx an...
Next-generation sequencing of circulating tumor DNA (ctDNA) is a non-invasive method to guide therapy selection for cancer patients. ctDNA variant allele frequency (VAF) is commonly reported and may aid in discerning whether a variant is germline or somatic. We report on the fidelity of VAF in ctDNA as a predictor for germline variant carriage. Two...
8579
Background: Thymic epithelial tumors (TET) are one of the rarest adult malignancies. Overall, patients have favorable survival outcomes, however a small subset develop metastatic disease. Genomic characterization of this very rare, clinically aggressive TET subset is lacking. Herein, we evaluated the clinical and genomic characteristics of met...
Simple Summary
More than 80% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia, characterized by loss of muscle and fat. However, most cachexia studies were predominantly focused on muscle. Our clinical study showed adipose tissue loss as a prognosticator in PDAC cachexia. Our study aims to understand the concurrent muscle an...
Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. Hypoxic regions within tumors represent sources of aggressiveness and resistance to therapy. Although long non-coding RNAs (lncRNAs) are increasingly recognized as major gene expression regulators, their regu...
The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathw...
BACKGROUND: Clinical whole‐exome sequencing (WES) has the potential to be repurposed for pharmacogenomics (PGx). However, accurately calling PGx alleles from WES remains challenging. In this study, we assessed the accuracy of Aldy, a computational tool, to call PGx star alleles and diplotypes from WES for 8 major PGx genes.
METHODS: Germline DNA w...
Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) is a non-invasive method to guide therapy selection for cancer patients. ctDNA variant allele frequency (VAF) is commonly reported and may aid in discerning whether a variant is germline or somatic. We report on the fidelity of VAF in ctDNA as a predictor for germline variant carriag...
Background: The PI3K pathway is dysregulated in the majority of triple-negative breast cancer (TNBCs), yet single agent inhibition of PI3K in TNBC has minimal clinical activity. We previously reported that PI3K inhibition leads to an immediate compensatory up-regulation of the Wnt pathway. Dual targeting of both pathways is highly synergistic again...
Background: Understanding how hereditary, lifestyle and demographic risk factors influence the development of breast cancer is critical for its prevention and treatment. For this purpose, the Susan G. Komen Tissue Bank at the IU Simon Comprehensive Cancer Center (KTB) serves as the world’s primary repository for normal breast tissue and blood sampl...
Background: Neoadjuvant chemotherapy (NAC) is a standard approach for many patients with triple negative breast cancer (TNBC). Our group, and others, have previously reported that the detection of circulating tumor DNA (ctDNA) after NAC and surgery is a surrogate for the presence of minimal residual disease (MRD) leading to inferior survival outcom...
The clinical challenge for treating HER2 (human epidermal growth factor receptor 2)–low breast cancer is the paucity of actionable drug targets. HER2-targeted therapy often has poor clinical efficacy for this disease due to the low level of HER2 protein on the cancer cell surface. We analyzed breast cancer genomics in the search for potential drug...
Colorectal cancer (CRC), a disease of high incidence and mortality, exhibits a large degree of inter- and intra-tumoral heterogeneity. The cellular etiology of this heterogeneity is poorly understood. Here, we generated and analyzed a single-cell transcriptome atlas of 49,859 CRC cells from 16 patients, validated with an additional 31,383 cells fro...
Purpose:
This retrospective analysis aims to determine the relationship between BMI and circulating tumor DNA (ctDNA) in triple negative breast cancer (TNBC). and to evaluate the impact of BMI on disease recurrence and survival in the homogeneous, high risk population of patients with residual TNBC after neoadjuvant chemotherapy.
Experimental des...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
PURPOSE
Identification of incidental germline mutations in the context of next-generation sequencing is an unintended consequence of advancing technologies. These data are critical for family members to understand disease risks and take action.
PATIENTS AND METHODS
A retrospective cohort analysis was conducted of 1,028 adult patients with metastat...
We hereby provide the initial portrait of lincNORS, a spliced lincRNA generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen...
p> Background: Two-thirds of patients with early-stage Triple-Negative Breast Cancer (TNBC) will harbor residual disease (RD) in the breast after neoadjuvant chemotherapy (NAC) and are at a high risk-of-recurrence. We and others have established the detection of minimal residual disease (MRD) as flagged by circulating tumor DNA (ctDNA) to be associ...
Importance
A significant proportion of patients with early-stage triple-negative breast cancer (TNBC) are treated with neoadjuvant chemotherapy. Sequencing of circulating tumor DNA (ctDNA) after surgery, along with enumeration of circulating tumor cells (CTCs), may be used to detect minimal residual disease and assess which patients may experience...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
e15555
Background: Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) is a non-invasive method to guide therapy selection for cancer patients. Identification of inherited germline cancer predisposition mutations that have significant implications for at-risk relatives may be missed during routine ctDNA testing. Allele frequency has t...
e15554
Background: The standard for tumor molecular profiling in precision oncology is the tissue-based biopsy. However, tissue biopsies are limited in the ability to capture the bulk of heterogeneity in advanced cancers. The integration of liquid biopsy diagnostics complementary to tissue-based sequencing may provide a broader perspective of heter...
Introduction: Circulating tumor cells (CTCs) represent a potent opportunity to glean important information about breast cancer biology using a non-invasive technique. However, EpCAM-based techniques are significantly limited by the presence of marker-negative CTCs, a phenotype that is enriched in the CTCs of metastatic triple-negative breast cancer...
Introduction: Triple negative breast cancer (TNBC) is a devastating disease responsible for a higher rate of morbidity and mortality compared to all other breast cancer subtypes. With few effective treatments, many have moved towards combination therapies. Using a genomically driven methodology, we show that Nuclear Protein 1 (NUPR1) is upregulated...
Background: A significant proportion of patients with early-stage TNBC are treated with neoadjuvant chemotherapy (NAC). Sequencing of ctDNA after surgery can be used to detect minimal residual disease and predict which patients may experience clinical recurrence. Methods: BRE12-158 is a recently completed Phase II clinical trial which randomized ea...
Background: Clinical DPYD testing is usually limited to targeted genotyping of a few known variants associated with severe toxicity to 5-fluorouracil (5-FU) or its prodrug capecitabine (CAPE). We present a 59 year old Indian woman diagnosed with metastatic colon cancer who was hospitalized with grade 4 mucositis and febrile neutropenia after 9 days...
The identification of cancer-predisposing germline variants has potentially substantial clinical impact for patients and their families. Although management guidelines have been proposed for some genes, guidelines for other genes are lacking. This review focuses on the current surveillance and management guidelines for the most common hereditary ca...
TPS472
Background: Adenocarcinoma of esophagus (EAC) and GEJ is the fastest rising cancer in the US. The outcomes are extremely poor with median overall survival (OS) being 12 mo in patients (pts) with metastatic disease. The standard first line treatment for metastatic EAC is platinum-based regimen with median progression free survival (PFS) of 6...
Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. Hypoxic regions within tumors represent sources of aggressiveness and resistance to therapy. Although long non-coding RNAs (lncRNAs) are increasingly recognized as major gene expression regulators, their regu...
Background:
Approximately two thirds of patients with localized triple-negative breast cancer (TNBC) harbor residual disease (RD) after neoadjuvant chemotherapy (NAC) and have a high risk-of-recurrence. Targeted therapeutic development for TNBC is of primary significance as no targeted therapies are clinically indicated for this aggressive subset....
Introduction: Circulating tumor DNA (ctDNA) has been shown in several studies to be a biomarker to predict tumor relapse and prognosis in breast cancer. However, the sensitivity of detection using ctDNA is modest in early-stage breast cancer and in patients with low-burden metastatic disease. Unlike ctDNA, which is released into circulation through...
Introduction: Circulating tumor cells (CTCs) represent a potent opportunity to glean important information about breast cancer biology using a non-invasive technique. However, EpCAM-based techniques are significantly limited by the presence of marker-negative CTCs, a phenotype that is enriched in the CTCs of metastatic triple-negative breast cancer...
Introduction: Triple negative breast cancer (TNBC) is a devastating disease responsible for a higher rate of morbidity and mortality compared to all other breast cancer subtypes. With few effective treatments, many have moved towards combination therapies. Using a genomically driven methodology, we show that Nuclear Protein 1 (NUPR1) is upregulated...
More than 50% of the human genome consists of transposable elements (TE), which mostly remain inactive and relatively stable in healthy individuals. These elements, commonly known as “jumping genes,” are sequences of DNA that are mobile and can change positions in the genome. However, only certain classes of retrotransposons (ALU, SVA, ERV and L1)...
Introduction: Circulating tumor DNA (ctDNA) has been shown in several studies to be a biomarker to predict tumor relapse and prognosis in breast cancer. However, the sensitivity of detection using ctDNA is modest in early-stage breast cancer and in patients with low-burden metastatic disease. Unlike ctDNA, which is released into circulation through...
Introduction: Triple negative breast cancer (TNBC) is a devastating disease responsible for a higher rate of morbidity and mortality compared to all other breast cancer subtypes. With few effective treatments, many have moved towards combination therapies. Using a genomically driven methodology, we show that Nuclear Protein 1 (NUPR1) is upregulated...
Introduction:Thymic epithelial tumors (TETs) are rare malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with myasthenia gravis, followed by thymic carcinoma which is less common but more clinically aggressive. The TCGA recently published a comprehensive analysis of 117 TETs using molecular profiling by...
More than 50% of the human genome consists of transposable elements (TE), which mostly remain inactive and relatively stable in healthy individuals. These elements, commonly known as “jumping genes,” are sequences of DNA that are mobile and can change positions in the genome. However, only certain classes of retrotransposons (ALU, SVA, ERV and L1)...
1581
Background: The identification of incidental germline mutations in the context of next-generation sequencing to guide therapy for cancer patients has become an unintended consequence of advancing technologies. While not the primary goal, additional information buried within the genomic data generated could be important for family members to be...
Background: The PI3K pathway is dysregulated in the majority of triple-negative breast cancer (TNBCs). Contrary to the theory of oncogene addiction, single agent inhibition of the PI3K pathway in TNBC has had only modest activity. Our group has demonstrated preclinically that when PI3K is inhibited, an immediate compensatory up-regulation of the Wn...
More than 50% of the human genome consists of transposable elements (TE). However only certain classes of retrotransposons (ALU, SVA, ERV and L1) are believed to be active. They transpose using an RNA intermediate causing target-site duplications along with a poly-A tail. They can also insert into intronic regions and disrupt normal transcription o...
Introduction: Circulating tumor cells (CTCs) represent a potent opportunity to glean important information about breast cancer biology in a non-invasive fashion. A current limitation to CTC analysis is the inability of positive-selection systems to capture EpCAM-low/negative CTCs, a phenotype that is enriched in the CTCs of metastatic triple negati...
Purpose
Mutations or copy number abnormalities of genes involved in homologous recombination (HR) occur in pancreatic ductal adenocarcinoma (PDAC). DNA-based measures of HR deficiency (HRD) have been developed and may help identify tumors with better response to DNA-damaging agents. This study aimed to describe the HR pathway mutations and HRD stat...
Heterozygous deletion of chromosome 17p (17p) is one of the most frequent genomic events in human cancers. Beyond the tumor suppressor TP53, the POLR2A gene encoding the catalytic subunit of RNA polymerase II (RNAP2) is also included in a ~20-megabase deletion region of 17p in 63% of metastatic castration-resistant prostate cancer (CRPC). Using a f...
Purpose:
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with lack of predictive biomarkers. We conducted a study to assess DNA damage repair (DDR) gene mutations as a predictive biomarker in PDAC patients treated with FOLFIRINOX.
Experimental design:
Indiana University Simon Cancer Center pancreatic cancer database was used to identi...
Citations
... We were the first group to define the role of RCC1 in PDAC 9 . Using CARIS database, DNA and RNA sequencing was performed on 5,071 PDAC tissues. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/467294301233154-1488423051685_Q64/Misako-Nagasaka.jpg)
... B7-H3 expression in healthy and malignant tissues has been extensively studied and reviewed since its discovery. While it is absent or expressed at very low levels in healthy tissues and body fluids, it is aberrantly expressed at high levels in cancer tissues in various malignancies [8,9,11,18]. Among healthy tissues, its mRNA levels are highest in the placenta, adipose tissue, cervix, endometrium, and adrenal glands, and protein levels are highest in the prostate, adipose tissue, adrenal gland, appendix, and breast [9,11]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/11431281188457711-1694623432503_Q64/Justin-Hwang.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/280126672654365-1443798811665_Q64/Emmanuel-Antonarakis.jpg)
... Multiple new RAF inhibitors have shown efficacy in vitro and are currently being investigated in phase I clinical trials: ERAS-254 (NCT05907304), DAY101 (NCT04985604), BGB-3245 (NCT04249843), KIN-2787 (NCT04913285), JZP815 (NCT05557045). Small molecules directly inhibiting ERK1/2, which target the MAPK pathway signaling downstream of both BRAF and RAS kinases, are also being studied in clinical trials, including BVD-523 (NCT04488003) and LY3214996 (NCT04534283) (159)(160)(161). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/930017940881410-1598744964629_Q64/Fadi-Taza.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/272663524409361-1442019458261_Q64/Mateusz-Opyrchal.jpg)
... Thus, a comprehensive understanding of these variations can lead to customized treatment options for Analysis of the correlation between the immune signatures of pancreatic cancer and PIM1, PIM2, and PIM3 revealed that PIM expression was significantly correlated with higher MAPK activation scores, T-cell inflammation scores, inflammatory markers, MHC class I and II gene expression, and various immune cell infiltrations. Thus, a comprehensive understanding of these variations can lead to customized treatment options for pancreatic cancers expressing PIM [97]. It is important to note that the connection between PIM3 kinase and immunotherapy may be critical for enhancing the efficacy of immunotherapy, and further studies are needed to fully understand the precise mechanisms and therapeutic implications and to provide valuable insights into the potential benefits and limitations of targeting PIM3 kinase in the context of immunotherapy. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1061423690027008-1630074536446_Q64/Sharon-Wu-18.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/312756438274049-1451578353738_Q64/Noel-Warfel.jpg)
... Alterations in genes that code for regulatory subunits of PIK3 have been detected in a tumorigenic TC cell line [64]. Interestingly, genomic alterations in TP53/CDK, EGFR/Ras, and PI3K/mTOR pathways have also been documented in metastatic TETs [65]. All these observations underscore the significance of the PIK3/Akt/mTOR pathway in TETs. ...
... Prior molecular testing noted elevated phospho-AKT activity and the downregulation of PTEN in WHO type A/AB in C19MC-positive thymomas compared with normal tissues [108]. Based on this data and the modest efficacy seen with everolimus, a single-arm phase 2 study evaluated buparlisib, which is a pan-PI3K inhibitor, in TET patients with relapsed or refractory disease [31]. Fourteen thymoma patients (WHO type B2/3) received 100 mg buparlisib daily. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/514260042485761-1499620556845_Q64/Mohammad-Abu-Zaid.jpg)
... We assessed if the regional epithelial programs that we spatially identified in mouse and are conserved in human are relevant to definition of human disease. To this end, we constructed pseudo-bulk profiles from epithelial cells for our mouse samples and for recently published human samples profiled along different stages of malignant transformation, from normal tissue to polyp to CRC (Becker et al., 2022;Che et al., 2021;Chen et al., 2021;Joanito et al., 2022;Khaliq et al., 2022a;Pelka et al., 2021;Zheng et al., 2022). We scored each epithelial pseudo-bulk profile with the differentially expressed genes between the epithelial parts of the regions and computed the principal components of these scores across all human and mouse samples (Methods). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/977363072471040-1610032923169_Q64/Ateeq-Khaliq-2.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/279609594662917-1443675530799_Q64/Cihat-Erdogan-2.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1185478413955072-1659651487154_Q64/Zeyneb-Kurt.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/11431281158422909-1684142202330_Q64/Sultan-Turgut.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/637636863594496-1529035883647_Q64/Ashiq-Masood.jpg)
... Gedatolisib (PKI-587) is a potent reversible dual inhibitor that selectively targets all class I PI3K isoforms and mTOR. A phase I trial enrolled 18 patients with advanced TNBC to investigate the safety of gedatolisib combined with cofetuzumab pelidotin, demonstrating that this combination had a good safety profile and promising clinical activity, which warrants further investigation to treat metastatic TNBC [58]. In another phase of the Ib trial, 107 patients with BC were treated with gedatolisib combined with docetaxel, cisplatin, or dacomitinib; 10% of evaluable patients (7/70) experienced dose-limiting toxicity, and the most common was grade 3 oral mucositis. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/746184385781765-1554915629251_Q64/Jeffrey-Solzak.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/11431281115337238-1674841273269_Q64/Chao-Wang-125.jpg)
... Studies describing the associations between CAF characteristics and CRC molecular subtypes or CRC gene mutations are sparse [49][50][51]. Recently, it was reported that consensus molecular subtype 4 (CMS4, mesenchymal type) [52] CRC has a high CAF content expressing DCN in their microenvironment [51]. ...
... These methods have primarily been validated using genetic reference material (e.g., cell lines from the Genetic Testing Materials Coordination Program [GeT-RM]) (14)(15)(16); however, in order to be suitable for clinical implementation, it is critical to verify the accuracy of computational genotype extraction methods using clinical NGS data derived from patient samples. Clinical NGS data can present numerous challenges that limit precise genotype determination, including low read depth, incomplete coverage of PGx-relevant loci, the inability to phase variants, and difficulty resolving large-scale structural variations (17). Computational genotyping methods have been iteratively developed towards the goal of overcoming these challenges, but their ability to accurately extract genotypes from clinical NGS data remains largely unestablished. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/279310381404164-1443604192545_Q64/Tyler-Shugg.jpg)
