Response to Abemaciclib and Immunotherapy Rechallenge with Nivolumab and Ipilimumab in a Heavily Pretreated TMB-H Metastatic Squamous Cell Lung Cancer with CDKN2A Mutation, PIK3CA Amplification and TPS 80%: A Case Report.

Inactivation of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene is considerably more frequent in squamous cell lung cancer (SqCLC) than in other subtypes of lung cancer and may be a promising target for this histology. Here, we present the course of diagnosis and treatment of a patient with advanced SqCLC, harboring not only CDKN2A mutation but also PIK3CA amplification, Tumor Mutational Burden-High (>10 mutations/megabase), and a Tumor Proportion Score of 80%. After disease progression on multiple lines of chemotherapy and immunotherapy, he responded favorably to treatment with the CDK4/6i Abemaciclib and later achieved a durable partial response to immunotherapy rechallenge with a combination of anti-PD-1 and anti-CTLA-4, nivolumab, and ipilimumab.

Increasing Stress to Induce Apoptosis in Pancreatic Cancer via the Unfolded Protein Response (UPR).

High rates of cell proliferation and protein synthesis in pancreatic cancer are among many factors leading to endoplasmic reticulum (ER) stress. To restore cellular homeostasis, the unfolded protein response (UPR) activates as an adaptive mechanism through either the IRE1α, PERK, or ATF6 pathways to reduce the translational load and process unfolded proteins, thus enabling tumor cells to proliferate. Under severe and prolonged ER stress, however, the UPR may promote adaptation, senescence, or apoptosis under these same pathways if homeostasis is not restored.

Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib.

Recent efforts to personalize treatment with platinum-based chemotherapy and PARP inhibitors have produced promising results in homologous recombinant deficient (HRD) metastatic pancreatic cancer (MPC). However, new strategies are necessary to overcome resistance. The below case series documents patients treated at the HonorHealth Research Institute with a diagnosis of HRD MPC who received Mitomycin C (MMC) treatment from January 2013 until July 2018.

Neoadjuvant chemotherapy or upfront surgery in localized pancreatic cancer: a contemporary analysis.

Neoadjuvant chemotherapy is considered a new treatment option for potentially resectable pancreatic cancer. However, data are not well established on overall survival and delaying surgery in resectable pancreatic cancer, as well as on those patients that ultimately cannot undergo surgery. We analyzed pancreatic cancer patients treated in a tertiary hospital from January 2016 to December 2020.

Disparities in Metabolic Conditions and Cancer Characteristics among Hispanic Women with Breast Cancer: A Multi-Institutional Study.

While the associations of common metabolic conditions with ethnicity have been previously described, disparity among Hispanic individuals based on country of origin is understudied. This multi-institutional analysis explored the prevalence of metabolic conditions and their association with cancer subtypes among Mexican and non-Mexican Hispanics. After IRB approval, we conducted a cross-sectional study at two academic medical centers with a significant Hispanic patient population (Texas Tech University Health Sciences Center, El Paso, TX (TTUHSC-EP) and Cleveland Clinic Florida in Weston, FL (CCF)).

Precision Medicine Targeting Genomic Alterations in Advanced Cholangiocarcinoma: Current State and Future Perspectives.

Although a relatively uncommon tumor, cholangiocarcinoma is on the rise globally. Of note, most patients are diagnosed with metastatic disease, and the prognosis is poor with cytotoxic chemotherapy. Strategies targeting specific genomic alterations have demonstrated promising activity in recent years and could represent a new therapeutic avenue for these patients.

Circulating Cell-Free Tumor DNA in Advanced Pancreatic Adenocarcinoma Identifies Patients With Worse Overall Survival.

Background: Plasma-based circulating cell-free tumor DNA (ctDNA) genomic profiling by next-generation sequencing (NGS)is an emerging diagnostic tool for pancreatic cancer (PC). The impact of detected genomic alterations and variant allele fraction (VAF) in tumor response to systemic treatments and outcomes is under investigation.

Methods: Patients with advanced PC who had ctDNA profiled at time of initial diagnosis were retrospectively evaluated.

Circulating Tumor DNA-Based Testing and Actionable Findings in Patients with Advanced and Metastatic Pancreatic Adenocarcinoma.

Purpose: Recent advances in molecular diagnostic technologies allow for the evaluation of solid tumor malignancies through noninvasive blood sampling, including circulating tumor DNA profiling (ctDNA). Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, often because of late presentation of disease. Diagnosis is often made using endoscopic ultrasound or endoscopic retrograde cholangiopancreatography, which often does not yield enough tissue for next-generation sequencing.

Infigratinib (BGJ398): an investigational agent for the treatment of FGFR-altered intrahepatic cholangiocarcinoma.

Introduction: The fibroblast growth factor receptor (FGFR) pathway is essential in cell proliferation, differentiation, migration, and survival. Cancers such as intrahepatic cholangiocarcinoma (IHCA) have demonstrated alterations of FGFR allowing unregulated growth. Infigratinib (BGJ398) is a potent ATP-competitive inhibitor of all four FGFR receptors as demonstrated by the consistently high prevalence of hyperphosphatemia, indicating disruption of FGFR-related phosphate homeostasis.

Bevacizumab in the neoadjuvant treatment of human epidermal growth factor receptor 2-negative breast cancer: A meta-analysis of randomized controlled trials.

Several randomized clinical trials have suggested the effectiveness of bevacizumab (Bev) in early and advanced breast cancer; however, due to the increased toxicity and lack of a clear long-term survival benefit, there is currently no defined role for Bev in breast cancer in the USA, while it has been approved in Europe. We herein sought to conduct a meta-analysis of large randomized trials comparing the efficacy and long-term outcome of neoadjuvant chemotherapy with Bev compared with chemotherapy without Bev in human epidermal factor receptor 2 (HER2)-negative breast cancer. A search was conducted through PubMed and Ovid Medline databases.

Spectrum of Gastrointestinal Manifestations in Joint Hypermobility Syndromes.

Joint hypermobility is a common, primarily benign finding in the general population. However, in a subset of individuals joint hypermobility causes a range of clinical problems mainly affecting the musculoskeletal system and, to a lesser extent, extra-articular disorders. Joint hypermobility often appears as a familial trait and is shared by several inherited connective tissue disorders, including the hypermobility subtype of Ehlers-Danlos syndrome (hEDS) and benign joint hypermobility syndrome (BJHS/JHS).

Disparities in breast cancer: a multi-institutional comparative analysis focusing on American Hispanics.

Unlabelled: Breast cancer (BC) is the leading cause of cancer death in Hispanic/Latino women nationwide. Hispanic women are more likely to be presented with advanced disease and adverse prognosis subtypes. The aim of this study is to describe the clinico- pathological characteristics and disparities in breast cancer in this group at two tertiary care University-based medical centers.

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma.

Background & Aims: Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC.

Methods: We performed a case-control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015.

Ultrasound-Assisted Catheter-Directed Thrombolysis: A Novel and Promising Endovascular Therapeutic Modality for Intermediate-Risk Pulmonary Embolism.

Intermediate-risk pulmonary embolism (PE), also known as submassive PE, occurs in a substantial group of patients and carries a significant mortality risk. With adequate risk stratification, catheter-directed techniques could be used as a therapeutic approach in the intermediate-risk PE. Ultrasound-assisted catheter-directed thrombolysis (UCDT) represents a novel endovascular technique with good clinical and safety outcomes.

Proteomics in cancer research: methods and application of array-based protein profiling technologies.

With the human genome sequence now determined, the field of molecular medicine is moving beyond genomics to proteomics, the large-scale analysis of proteins. It is now possible to examine the expression of more than 1000 proteins using mass spectrometry technology coupled with various separation methods. Microarray technology is a new and efficient approach, for extracting relevant biomedical data and has a wide range of applications.

Cutaneous aneurysmal fibrous histiocytoma with a t(12;19)(p12;q13) as the sole cytogenetic anomaly.

We report a case of a 39-year-old woman with a recurrent aneurysmal fibrous histiocytoma of the right lower leg. Cytogenetic analysis of the tumor specimen disclosed a 46,XX,t(12;19)(p12;q13) karyotype. Multicolor fluorescence in situ hybridization (M-FISH), followed by conventional FISH analysis, confirmed the reciprocal translocation as the sole cytogenetic anomaly, and allowed for the positioning of chromosomes 12 and 19 breakpoints proximal to the BCL3 gene and between ETV6 and PIK3C2G gene loci, respectively.