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Molecular targets in GI malignancies - A pathologist's perspective
1Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
Abstract:
Newer molecular diagnostics and improved understanding of cancer pathogenesis have identified multiple pathways that can be potentially targeted with the use of novel therapeutics in development. These developments have ushered cancer therapeutics in newer era of personalized medicine. Same is reflected on current management strategies for advanced gastrointestinal malignancies. Molecular profiling for BRAF and RAS is standard for colorectal cancer while Her2 and PDL1 status is needed for planning therapy of advanced gastroesophageal cancers. Tissue agnostic markers like MSI, TMB and NTRK are making headways in therapeutic armamentarium. While newer targeted therapies against FGFR, EGFR, PI3K-AKT, DDR pathways are showing promising results in initial studies. Here we review traditional as well as upcoming molecular markers in field of GI malignancies, methods of testing and evidence for rational use in clinical practice.
Insights
Advanced gastrointestinal cancer treatment is evolving with personalized medicine. Molecular profiling identifies key targets like BRAF, RAS, Her2, and PDL1, guiding novel targeted therapies for better patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Advances in molecular diagnostics and cancer pathogenesis reveal new therapeutic targets.
- Personalized medicine is transforming cancer treatment strategies, particularly for advanced gastrointestinal (GI) malignancies.
Purpose of the Study:
- To review established and emerging molecular markers for GI malignancies.
- To discuss testing methodologies and evidence supporting their clinical application.
Main Methods:
- Literature review of molecular diagnostics in GI cancer.
- Analysis of current therapeutic strategies based on molecular profiling.
- Evaluation of novel targeted therapies and their pathways.
Main Results:
- Standard molecular profiling includes BRAF/RAS for colorectal cancer and Her2/PDL1 for gastroesophageal cancers.
- Tissue-agnostic markers such as microsatellite instability (MSI), tumor mutational burden (TMB), and NTRK are increasingly utilized.
- Emerging targeted therapies show promise against FGFR, EGFR, PI3K-AKT, and DNA Damage Response (DDR) pathways.
Conclusions:
- Molecular markers are crucial for personalized treatment of advanced GI cancers.
- A comprehensive understanding of these markers and testing methods is essential for clinical practice.
- Ongoing research into novel targeted therapies holds significant potential for improving patient care.
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