Further characterization of thymic epithelial tumors (TETs) is needed. Genomic information from 102 evaluable TETs from The Cancer Genome Atlas (TCGA) dataset and from the IU-TAB-1 cell line (type AB thymoma) underwent clustering analysis to identify molecular subtypes of TETs. Six novel molecular subtypes (TH1-TH6) of TETs from the TCGA were identified, and there was no association with WHO histologic subtype.
A randomized trial in glioblastoma patients with methylated-MGMT (m-MGMT) found an improvement in median survival of 16.7 months for combination therapy with temozolomide (TMZ) and lomustine, however the approach remains controversial and relatively under-utilized. Therefore, we sought to determine whether comprehensive genomic analysis can predict which patients would derive large, intermediate, or negligible benefits from the combination compared to single agent chemotherapy.
The Cellworks Singula Therapeutic Response Index (TRI) has been developed to assist clinicians and GBM patients in choosing between competing therapeutic options. In contrast to approaches that consider single aberrations, which often yield limited benefit, Cellworks utilizes an individual patient’s next generation sequencing results and a mechanistic multi-omics biology model, the Cellworks Omics Biology Model (CBM), to biosimulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells.
The Cellworks Singula Therapeutic Response Index (TRI) has been developed to assist clinicians and NSCLC patients in choosing between competing therapeutic options. In contrast to approaches that consider single aberrations, which often yield limited benefit, Cellworks utilizes an individual patient’s next generation sequencing results and a mechanistic multi-omics biology model, the Cellworks Omics Biology Model (CBM), to biosimulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells.
ATRA combined with arsenic trioxide revolutionized the treatment of APL. Based on promising in vitro data, several clinical trials evaluated ATRA combinations in non-APL AML, in which some patients seemed to benefit from the addition. Thus, predicting response a priori is imperative to determine the optimal treatment for each patient. The CBM was used to evaluate the impact of initial therapy with ATRA combined with cytarabine, etoposide, idarubicin (ATRA-CEI) to assess the biomarkers responsible for response in adults with AML.
Paclitaxel and carboplatin (PC) is used to treat a wide variety of malignancies including gynecologic, breast, lung, and occult primary cancers. In NSCLC, PC led to a substantial improvement in 1-yr survival from 10% (P alone) to approximately 50% seen with the combination.
Using a 5FU backbone, a variety of combination chemotherapy regimens have been adopted for gastric cancer. However, the genetic heterogeneity of the disease suggests certain drugs would lead to better outcomes for specific patients. In principle, the incorporation of molecular profiling information into treatment selection can generate superior survival for patients. Therefore, we conducted a pilot study using the CBM to identify novel genomic biomarkers of response and resistance to several 5FU-based regimens.
Cancer management using cytotoxic drugs is hampered by limited efficacy. Hence, a personalized treatment approach matching chemotherapy with appropriate patients remains a persistent and unmet need in the clinic. Genomic heterogeneity among patients creates an opportunity to discern key genomic aberrations and pathways that confer resistance and response to standard treatment options.