Application Of Molecular Profiling Research Articles

Application of Molecular Profiling in Colorectal Cancer Surgery.

Although molecular profiling has long been integrated into the systemic therapy of metastatic colorectal cancer, it did not arouse enough attention in colorectal cancer surgery until Cercek's study showing that microsatellite instability-high (MSI-H) rectal cancer might be cured by anti-PD-1 therapy. With the advance of precision medicine, we are getting closer to understand the nature of colorectal cancer, the relationship between molecular profiling and phenotype, and its impact on surgical management of colorectal cancer.

Molecular profiling (MP) for malignancies: Knowledge gaps and variable practice patterns among United States oncologists (Onc).

10510 Background: Clinically impactful therapies for malignancies require the identification of specific molecular alterations. Onc must be aware of these targets and how to interpret them to provide optimum care. The use of MP has become the standard of care for many cancers, and is recently FDA approved. Using 2 data sets, we assessed the current awareness and incorporation of MP in the treatment of cancer; comparing data from community based Onc (C) to academic Onc (A). Methods: C consisted of 292 physicians polled using an audience response system during 6 case-based research events across the US. Questions focused on various aspects of molecular testing. Data for A was obtained from a chart review focused on timing and extent of MP in disease specific academic practices (lung, breast, GI) (N = 59). Results: Within C, 257 (88%) were Onc from community-based practices. The frequency at which Onc ordered MP significantly varied depending on tumor type; 33% in lung cancer (LC), 18% in colorectal cancer (CRC) and less commonly in breast cancer (BC) (8%). In A, MP was ordered more frequently; 74% in LC, 27% in CRC and 0% in BC. These results reflect a gap in practice among community versus academic Onc, as C had lower utilization of MP for both LC and CRC. In C, Onc were also asked to match the molecular alteration with the appropriate targeted therapy. Onc incorrectly matched the molecular alteration to the targeted therapy or marked unknown in up to 69%. This reflects a large knowledge gap among community Onc with regards to the correct application of MP to currently FDA approved targeted therapies. Conclusions: Given the significant knowledge and practice gap, we conclude there is an urgent need for focused educational activities that facilitate improved knowledge of MP and corresponding personalized therapeutic strategies for Onc in the US.

Molecular profile in breast cancer

Over recent decades breast cancer research has undergone a real revolution thanks to the emergence of novel technologies based on high throughput gene expression analysis. Gene-expression profiling has made a significant contribution to our understanding of breast cancer biology, and clinical researchers have moved from “semantic” classification of breast cancer subclasses by pathology-based biomarkers (e.g. estrogen receptor, progesterone receptor and HER2 status) into new genomic classifiers. The terminology of intrinsic subtypes was adopted by the 2011 St. Gallen Consensus Conference to describe the paradigm for making treatment decisions in patients with breast cancer. Apart from expanding prognostic knowledge, the application of molecular profiling will allow prediction of treatment efficacy and forecasting of outcomes for individual patients with breast cancer. Currently available tests include Oncotype DX™, NanoString PAM50 test (Prosigna®), MammaPrint® and EndoPredict. Prospective clinical trials adding these tests are currently ongoing.

Application of molecular profiling in clinical trials for advanced metastatic cancers.

There is growing interest in the application of molecular profiling, including sequencing, genotyping, and/or mRNA expression profiling, to the analysis of patient tumors with the objective of applying these data to inform therapeutic choices for patients with advanced cancers. Multiple clinical trials that are attempting to validate this personalized or precision medicine approach are in various stages of development and execution. Although preliminary data from some of these efforts have fueled excitement about the value and utility of these studies, their execution has also provoked many questions about the best way to approach complicating factors such as tumor heterogeneity and the choice of which genetic mutations to target. This commentary highlights some of the challenges confronting the clinical application of molecular tumor profiling and the various trial designs being utilized to address these challenges. Randomized trials that rigorously test patient response to molecularly targeted agents assigned based on the presence of a defined set of mutations in putative cancer-driving pathways are required to address some of the current challenges and to identify patients likely to benefit from this approach.

Breast cancer expression profiling: the impact of microarray testing on clinical decision making

The available clinical prognostic tools show an obvious limitation in predicting the outcome of breast cancer patients, and pathological features cannot classify tumours accurately. Microarray-based molecular classification of breast tumours or selection of gene expression panels to improve risk prediction or treatment outcomes are thought to be theoretically superior to established clinical and pathological criteria, based on guidelines such as the St Gallen and National Institute of Health consensus, or which use specific prognostic tools, such as the Nottingham Prognostic Index or Adjuvant-Online algorithm. Although two diagnostic tests based on gene expression profiling of breast cancer are commercially available, a new molecular classification and molecular forecasting of breast cancer based on expression profiling cannot outperform the standard tumour diagnostic at present. This review focuses on some important problems in the practical application of molecular profiling of breast cancer for clinical purposes.