Dissecting the Spatially Restricted Effects of Microenvironment-Mediated Resistance on Targeted Therapy Responses.

The response of tumors to anti-cancer therapies is defined not only by cell-intrinsic therapy sensitivities but also by local interactions with the tumor microenvironment. Fibroblasts that make tumor stroma have been shown to produce paracrine factors that can strongly reduce the sensitivity of tumor cells to many types of targeted therapies. Moreover, a high stroma/tumor ratio is generally associated with poor survival and reduced therapy responses.

Conventional Therapies of Oral Cancers: Highlights on Chemotherapeutic Agents and Radiotherapy, Their Adverse Effects, and the Cost Burden of Conventional Therapies.

Oral cancer (OC) is increasing worldwide, and it is mostly present to clinic in the late-stage of disease. Cancer of the lips, tongue, hard palate, upper and lower gingiva, buccal mucosa, and retromolar trigone are all included in the category of oral cavity cancer. Disease symptomatology and pathological grading decides the course of treatment.

Molecular determinants of outcomes in relapsed or refractory mantle cell lymphoma treated with ibrutinib or temsirolimus in the MCL3001 (RAY) trial.

Mantle cell lymphoma (MCL) is a rare, incurable lymphoma subtype characterized by heterogeneous outcomes. To better understand the clinical behavior and response to treatment, predictive biomarkers are needed. Using residual archived material from patients enrolled in the MCL3001 (RAY) study, we performed detailed analyses of gene expression and targeted genetic sequencing.

Integrating mutational and nonmutational mechanisms of acquired therapy resistance within the Darwinian paradigm.

Mutational processes and nongenetic phenotypic state transitions represent distinct paradigms for understanding acquired resistance to targeted therapies. While ample empirical evidence supports both paradigms, they are typically viewed as mutually exclusive. However, a growing body of evidence points to the multifactorial nature of resistance, where resistant tumor cell phenotypes integrate the influence of multiple mutational and epigenetic changes.

Identifying key questions in the ecology and evolution of cancer.

The application of evolutionary and ecological principles to cancer prevention and treatment, as well as recognizing cancer as a selection force in nature, has gained impetus over the last 50 years. Following the initial theoretical approaches that combined knowledge from interdisciplinary fields, it became clear that using the eco-evolutionary framework is of key importance to understand cancer. We are now at a pivotal point where accumulating evidence starts to steer the future directions of the discipline and allows us to underpin the key challenges that remain to be addressed.

Cancers from Novel -Mutant Mouse Models Provide Insights into Polymerase-Mediated Hypermutagenesis and Immune Checkpoint Blockade.

mutations are a major cause of hypermutant cancers, yet questions remain regarding mechanisms of tumorigenesis, genotype-phenotype correlation, and therapeutic considerations. In this study, we establish mouse models harboring cancer-associated mutations P286R and S459F, which cause rapid albeit distinct time to cancer initiation , independent of their exonuclease activity. Mouse and human correlates enabled novel stratification of mutations into three groups based on clinical phenotype and mutagenicity.

Combined Cell-free DNA and RNA Profiling of the Androgen Receptor: Clinical Utility of a Novel Multianalyte Liquid Biopsy Assay for Metastatic Prostate Cancer.

Background: The androgen receptor (AR) remains a critical driver in metastatic castration-resistant prostate cancer (mCRPC). Profiling AR aberrations in both circulating DNA and RNA may identify key predictive and/or prognostic biomarkers in the context of contemporary systemic therapy.

Objective: To profile AR aberrations in circulating nucleic acids and correlate with clinical outcomes.

Resistance to targeted therapies as a multifactorial, gradual adaptation to inhibitor specific selective pressures.

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 evolution of resistance to different clinical ALK inhibitors.

Aberrant Superficial Branch of the Radial Nerve-Radial Forearm Free Flap Considerations.

The superficial branch of the radial nerve (SBRN) is encountered and must be preserved during the harvest of a radial forearm free flap (RFFF). An abnormal course of the SBRN was encountered during the harvest of an RFFF. The nerve had an abnormal course with two branches-in the proximal forearm, one branch was anterior and the second branch was posterior to the brachioradialis muscle and in the distal forearm, both of these nerves merged together.

Metabolic Profiling of healthy and cancerous tissues in 2D and 3D.

Metabolism is a compartmentalized process, and it is apparent in studying cancer that tumors, like normal tissues, demonstrate metabolic cooperation between different cell types. Metabolic profiling of cells in 2D culture systems often fails to reflect the metabolism occurring within tissues in vivo due to lack of other cell types and 3D interaction. We designed a tooling and methodology to metabolically profile and compare 2D cultures with cancer cell spheroids, and microtissue slices from tumors, and normal organs.

Stability of open pathways.

We consider the steady state of an open biochemical pathway, with controlled flow. Previously we have shown that the steady state of open enzyme catalysed reactions may be unstable, which discourages the application of the quasi-steady-state approximation (QSSA) [IEE Proc.-Syst.