Chemotherapy Response In Cancer Patients Research Articles

PathCHEMO, a generalizable computational framework uncovers molecular pathways of chemoresistance in lung adenocarcinoma

Despite recent advances in discovering a wide array of novel chemotherapy agents, identification of patients with poor and favorable chemotherapy response prior to treatment administration remains a major challenge in clinical oncology. To tackle this challenge, we present a generalizable genome-wide computational framework pathCHEMO that uncovers interplay between transcriptomic and epigenomic mechanisms altered in biological pathways that govern chemotherapy response in cancer patients. Our approach is tested on patients with lung adenocarcinoma who received adjuvant standard-of-care doublet chemotherapy (i.e., carboplatin-paclitaxel), identifying seven molecular pathway markers of primary treatment response and demonstrating their ability to predict patients at risk of carboplatin-paclitaxel resistance in an independent patient cohort (log-rank p-value = 0.008, HR = 10). Furthermore, we extend our method to additional chemotherapy-regimens and cancer types to demonstrate its accuracy and generalizability. We propose that our model can be utilized to prioritize patients for specific chemotherapy-regimens as a part of treatment planning.

Extraction of Aqueous Metabolites from Cultured Adherent Cells for Metabolomic Analysis by Capillary Electrophoresis-Mass Spectrometry.

Metabolomic analysis is a promising omics approach to not only understand the specific metabolic regulation in cancer cells compared to normal cells but also to identify biomarkers for early-stage cancer detection and prediction of chemotherapy response in cancer patients. Preparation of uniform samples for metabolomic analysis is a critical issue that remains to be addressed. Here, we present an easy and reliable protocol for extracting aqueous metabolites from cultured adherent cells for metabolomic analysis using capillary electrophoresis-mass spectrometry (CE-MS). Aqueous metabolites from cultured cells are analyzed by culturing and washing cells, treating cells with methanol, extracting metabolites, and removing proteins and macromolecules with spin columns for CE-MS analysis. Representative results using lung cancer cell lines treated with diamide, an oxidative reagent, illustrate the clearly observable metabolic shift of cells under oxidative stress. This article would be especially valuable to students and investigators involved in metabolomics research, who are new to harvesting metabolites from cell lines for analysis by CE-MS.