Re-establishing Responsiveness in a Case of Refractory Metastatic Rectal Cancer with a Personalized de novo Combination Regimen

Introduction: Encyclopedic Tumor Analysis (ETA) is multi-analyte, molecular and functional interrogation to identify latent vulnerabilities in solid tumors which can then be targeted in organ- and label-agnostic combination treatment regimens.Case Presentation: We describe here a case of metastatic rectal cancer in a 61-year-old male who was progressed on all prior Standard of Care (SoC) treatment modalities including surgery, chemotherapy and radiotherapy. We addressed disease recurrence via personalized therapy guided by ETA which revealed characteristic molecular heterogeneity in primary and metastatic lesions in terms of single nucleotide variations (SNVs) and gene copy number variations (CNVs).  Notably, a novel TBL1XR1 (Exon1) – PIK3CA (Exon 2) gene fusion was identified in the tumor along with gene copy number gains in TERT, IGF-1R, MYC, FGFR1 and EGFR genes.Conclusion: ETA based molecular analysis with synchronous in vitro chemo-sensitivity profiling strategy helped to define de novo combinatorial therapy regimen of targeted and cytotoxic drugs which countered disease progression at each instance and led to the durable regression of primary as well as metastatic lesions

Unveiling the Enigma of the Phosphatase and Tensinogen Gene in Cancer and its Potential Role in Oral Cancer- A Narrative Review

Phosphatase and Tensin Homolog (PTEN) is a tumour suppressor gene that plays a vital role in the normal cell cycle. PTEN acts on the cell via the phosphatidyl-inositol-3-kinase pathway which is involved in the process of cell growth, differentiation, migration, and survival. PTEN is most frequently inactivated in human cancers, because of genetic alterations or transcriptional/post-transcriptional modifications. Literature search was done using the keywords “PTEN in cancer” and “PTEN in Oral Cancer” using Pubmed as the database. This article briefly discusses the multiple features of the PTEN gene and its significance in cancer for improving the understanding of the biology of oral carcinogenesis and the potential for future research in this field

URSODEOXYCHOLIC ACID: REMARKABLE DERIVATIVE AS LIVER PROTECTANT

<p>Ursodeoxycholic acid is a choleretic. Ursodeoxycholic acid responsible for raising bile production in body and ultimately bile is necessary for the breakdown of lipids. Additionally, bile is responsible for removal body's toxin. In addition to its choleretic effect, ursodeoxycholic acid also has anti-inflammatory and antioxidant properties. This characteristic may help in preventing liver injury and promoting repair. Additionally, ursodeoxycholic acid has been demonstrated to have cytoprotective properties, which implies that it may aid in preventing the death of liver cells. People who have liver problems that cause bile to build up may benefit from ursodeoxycholic acid's ability to increase bile flow. It helps the liver by various complementary mechanisms. It helps the liver by its cytoprotective, Immunomodulatory, and Anti apoptotic. A non-toxic, hydrophilic bile acid called ursodeoxycholic acid (ursodiol) is used mostly to treat cholestatic liver diseases. It improves the biochemical parameters in various diseases and widely used in treatment of Primary biliary cirrhosis, Primary sclerosing cholangitis, Intrahepatic cholestasis of pregnancy, Cystic fibrosis, but furthermore studies are need to be done in clinical uses. The only medication authorized for use as the first-line treatment for PBC is ursodeoxycholic acid (UCDA). Overall, ursodeoxycholic acid is a potent molecule with a wide range of beneficial effects on the liver. The ability of ursodeoxycholic acid to treat various liver conditions, including alcoholic liver disease and hepatitis C, is currently being researched. This review summarizes the current understanding of the ursodeoxycholic acid mechanisms of action and offers data from clinical studies on its application to chronic liver disorders.</p&gt

Development and validation of a multigene variant profiling assay to guide targeted and immuno therapy selection in solid tumors.

We present data on analytical validation of the multigene variant profiling assay (CellDx) to provide actionable indications for selection of targeted and immune checkpoint inhibitor (ICI) therapy in solid tumors. CellDx includes Next Generation Sequencing (NGS) profiling of gene variants in a targeted 452-gene panel as well as status of total Tumor Mutation Burden (TMB), Microsatellite instability (MSI), Mismatch Repair (MMR) and Programmed Cell Death-Ligand 1 (PD-L1) respectively. Validation parameters included accuracy, sensitivity, specificity and reproducibility for detection of Single Nucleotide Alterations (SNAs), Copy Number Alterations (CNAs), Insertions and Deletions (Indels), Gene fusions, MSI and PDL1. Cumulative analytical sensitivity and specificity of the assay were 99.03 (95% CI: 96.54-99.88) and 99.23% (95% CI: 98.54% - 99.65%) respectively with 99.20% overall Accuracy (95% CI: 98.57% - 99.60%) and 99.7% Precision based on evaluation of 116 reference samples. The clinical performance of CellDx was evaluated in a subsequent analysis of 299 clinical samples where 861 unique mutations were detected of which 791 were oncogenic and 47 were actionable. Indications in MMR, MSI and TMB for selection of ICI therapies were also detected in the clinical samples. The high specificity, sensitivity, accuracy and reproducibility of the CellDx assay is suitable for clinical application for guiding selection of targeted and immunotherapy agents in patients with solid organ tumors