Role of gene expression in colorectal cancer: a comprehensive molecular profiling study.

Background: In patients with colorectal cancer (CRC), the therapeutic effects of conventional immune checkpoint inhibitors targeting the adaptive immune system are largely limited to those with microsatellite instability-high tumors. Meanwhile, new immunotherapies targeting the innate immune system are attracting increasing attention. CD47 is a representative innate immune checkpoint involved in the evasion of tumor cell phagocytosis by macrophages.

Large-scale analysis of CDH1 mutations defines a distinctive molecular subset with treatment implications in gastric cancer.

Although histological and molecular classifications have been extensively studied for gastric cancer (GC), targeted therapies for GC remain limited. CDH1 mutations (MT) are characteristic of genomically stable GC and are associated with poor prognosis, but lack effective or targeted therapies. Here, we showed the overall mutation frequency of CDH1 was 9.

Predictive value of CDC37 gene expression for targeted therapy in metastatic colorectal cancer.

Background: CDC37 is a key determinant of client kinase recruitment to the HSP90 chaperoning system. We hypothesized that kinase-specific dependency on CDC37 alters the efficacy of targeted therapies for metastatic colorectal cancer (mCRC).

Material And Methods: Two independent mCRC cohorts were analyzed to compare the survival outcomes between CDC37-high and CDC37-low patients (stratified by the median cutoff values): the CALGB/SWOG 80405 trial (226 and 207 patients receiving first-line bevacizumab- and cetuximab-containing chemotherapies, respectively) and Japanese retrospective (50 refractory patients receiving regorafenib) cohorts.

Addressing barriers to increased adoption of DPYD genotyping at a large multisite cancer center.

Purpose: To describe the implementation of an in-house genotyping program to detect genetic variants linked to impaired dihydropyrimidine dehydrogenase (DPD) metabolism at a large multisite cancer center, including barriers to implementation and mechanisms to overcome barriers to facilitate test adoption.

Summary: Fluoropyrimidines, including fluorouracil and capecitabine, are commonly used chemotherapy agents in the treatment of solid tumors, such as gastrointestinal cancers. DPD is encoded by the DPYD gene, and individuals classified as DPYD intermediate and poor metabolizers due to certain genetic variations in DPYD can experience reduced fluoropyrimidine clearance and an increased risk of fluoropyrimidine-related adverse events.

COVID-19 vaccine uptake trends in SARS-CoV-2 previously infected cancer patients.

Purpose: Cancer patients are at high risk of developing severe illness from SARS-CoV-2 infection, but risk is lowered with receipt of COVID-19 vaccine. COVID-19 vaccination uptake among previously infected cancer patients may be influenced by an assumption of natural immunity, predicted weak immune response, or concerns about vaccine safety. The objective of this study was to evaluate COVID-19 vaccine uptake trends in cancer patients previously infected with SARS-CoV-2.

Impact of a Clinical Genomics Program on Trial Accrual for Targeted Treatments: Practical Approach Overcoming Barriers to Accrual for Underserved Patients.

Purpose: Clinical trials of novel and targeted agents increasingly require biomarkers for eligibility. Precision oncology continues to evolve, but challenges hamper broad use of molecular profiling (MP) that could increase the number of patients benefiting from targeted therapy. We implemented an integrated clinical genomics program (CGP), including a virtual Molecular Tumor Board (MTB), and examined its impact on MP use and impact on clinical trial accrual in a multisite regional-based cancer system with an emphasis on effects for isolated clinicians.

Landscape of , Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in -Mutated Cancers.

Purpose: Promising single-agent activity from sotorasib and adagrasib in -mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of -variant prevalence, genomic alterations, and the relationship between and immuno-oncology biomarkers is lacking.

Materials And Methods: Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed.

Molecular characterization of squamous cell carcinoma of the anal canal.

Background: Squamous cell carcinoma of the anal canal (SCCA) is an uncommon malignancy with limited therapeutic options. Nivolumab and pembrolizumab show promising results in patients with SCCA. Human papillomavirus (HPV)-negative tumors are frequently -mutated (MT) and often resistant to therapy.

Molecular characteristics and clinical outcomes of patients with Neurofibromin 1-altered metastatic colorectal cancer.

Loss-of-function alterations of Neurofibromin 1 (NF1) activate RAS, a driver of colorectal cancer. However, the clinical implications of NF1 alterations are largely unknown. We performed a comprehensive molecular profiling of NF1-mutant colorectal cancer using data from 8150 patients included in a dataset of commercial CLIA-certified laboratory (Caris Life Sciences).

Association of Homologous Recombination-DNA Damage Response Gene Mutations with Immune Biomarkers in Gastroesophageal Cancers.

The prevalence of homologous recombination-DNA damage response (HR-DDR) genetic alterations is of therapeutic interest in gastroesophageal cancers. This study is a comprehensive assessment of HR-DDR mutation prevalence across gastroesophageal adenocarcinomas and squamous cell carcinomas. Here we investigate the association of HR-DDR mutations with known predictors for immune-checkpoint inhibition [deficiency in mismatch-repair (dMMRP), tumor mutational burden (TMB), and programmed death ligand 1 (PD-L1)].

Impact of Sociodemographic Disparities and Insurance Status on Survival of Patients with Early-Onset Colorectal Cancer.

Background: Low socioeconomic status (SES) has been linked to worse survival in patients with colorectal cancer (CRC); however, the impact of SES on early-onset CRC remains undescribed.

Materials And Methods: Retrospective analysis of data from the National Cancer Database (NCDB) between 2004 and 2016 was conducted. We combined income and education to form a composite measure of SES.

Large-scale analysis of KMT2 mutations defines a distinctive molecular subset with treatment implication in gastric cancer.

Frequent mutations of genes in the histone-lysine N-methyltransferase 2 (KMT2) family members were identified in gastric cancers (GCs). Understanding how gene mutations of KMT2 family affect cancer progression and tumor immune microenvironment may provide new treatment strategies. A total of 1245 GCs were analyzed using next-generation sequencing, whole transcriptome sequencing, immunohistochemistry (Caris Life Sciences, Phoenix, AZ).

The Landscape of Alterations in DNA Damage Response Pathways in Colorectal Cancer.

Purpose: Defective DNA damage response (DDR) is a hallmark of cancer leading to genomic instability and is associated with chemosensitivity. Although the mismatch repair system has been extensively studied, the clinical implications of other mechanisms associated with DDR alterations in patients with colorectal cancer remain unclear. This study aimed to understand DDR pathways alterations and their association with common clinical features in patients with colorectal cancer.

The treatment sequence may matter in patients undergoing pancreatoduodenectomy for early stage pancreatic cancer in the era of modern chemotherapy.

Background: The aim of this study was to investigate outcomes associated with neoadjuvant chemotherapy in patients undergoing pancreatoduodenectomy for early stage pancreatic adenocarcinoma in the era of modern chemotherapy.

Methods: The National Cancer Database (2010-2016) was queried for patients with clinical stage 0-2 pancreatic adenocarcinoma who underwent pancreatoduodenectomy. Patients who underwent up-front pancreatoduodenectomy were propensity matched to patients who received neoadjuvant chemotherapy.

Molecular Characterization of Appendiceal Goblet Cell Carcinoid.

Goblet cell carcinoid (GCC) is a distinct subtype of appendiceal neoplasm that exhibits unique clinical and pathologic features. We aimed to reveal the molecular profiles of GCC compared with other appendiceal tumors, such as adenocarcinomas and neuroendocrine tumors. A total of 495 appendiceal tumor samples (53 GCCs, 428 adenocarcinomas, and 14 neuroendocrine tumors) were tested with next-generation sequencing (NGS) on a 592-gene panel and IHC.

Comprehensive Genomic Profiling of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs).

Purpose: GEP-NENs are rare malignancies with increasing incidence. Their molecular characteristics are still undefined. We explored the underlying biology of GEP-NENs and the differences between gastrointestinal (GI) and pancreatic (PNEN), high-grade (HG), and low-grade (LG) tumors.

A Phase I/II Study of Veliparib (ABT-888) in Combination with 5-Fluorouracil and Oxaliplatin in Patients with Metastatic Pancreatic Cancer.

Purpose: Up to 17% of patients with pancreatic ductal adenocarcinoma (PDAC) harbor pathogenic (germline or somatic) mutations in a homologous recombination, DNA damage response and repair (HR-DDR) gene, such as , or . Platinum-based chemotherapy, or treatment with PARP inhibitors are of particular benefit in these patients. However, there may be even greater benefit when platinums and PARP inhibitors are combined.

Advances in borderline resectable pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is one of the most lethal cancers in oncology. Pancreatic cancer is the third most common cause of cancer-related mortality in the United States. As the years have progressed, the importance of a multidisciplinary and multimodal approach to pancreatic cancer care has been recognized and is now recommended in all major society guidelines.

Conversion therapy for intrahepatic cholangiocarcinoma and tumor downsizing to increase resection rates: A systematic review.

Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant neoplasm with dismal outcomes. Several therapeutic modalities have been used with variable success to downsize these tumors for resection. Neoadjuvant therapy such as chemoembolization and radioembolization offer promising options to manage tumor burden prior to resection.

Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma.

Background And Objectives: Peritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined.

Methods: We compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next-generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational burden (TMB).

Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets.

Background: Biliary tract cancers (BTCs) are a heterogeneous group of aggressive, rare malignancies with limited standard chemotherapeutic options for advanced disease. Recent studies have demonstrated potential novel biliary cancer targets and a possible role for immunotherapy in the treatment of patients with this disease. Intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), and gallbladder carcinoma (GBC) are frequently grouped together in clinical trials despite differences in tumor biology.