Epigenetics/Therapeutic Targets in Gastrointestinal Cancers

International Collaborative Research Review Article Published in Drug Discovery Today

Sarfraz Ahmad, PhD
AdventHealth Cancer Institute

Ganji P. Nagaraju¹, Prameswari Kasa², Begum Dariya³, Nagalakshmi Surepalli⁴, Sujatha Peela⁵, Sarfraz Ahmad⁶

¹Department of Hematology & Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30332, USA; ²Dr L. V. Prasad Diagnostics & Research Laboratory, Khairtabad, Hyderabad 500004, India; ³Department of Biosciences & Biotechnology, Banasthali University, Banasthali 304022, India; ⁴Dr. B. R. Ambedkar Open University, Hyderabad 500033, India; ⁵Department of Biotechnology, Dr. B..R. Ambedkar University, Srikakulam 532410, India; ⁶AdventHealth Cancer Institute, Orlando, FL 32804, USA

Gastrointestinal (GI) malignancies account for substantial mortality and morbidity worldwide. GI cancers are complex disease, resulting from genetic, epigenetic alterations, and environmental factors. They are generally promoted by dysregulated signal transduction and epigenetic pathways, which are controlled by specific enzymes.

Recent studies demonstrated that histone deacetylases (HDACs) together with DNA methyltransferases (DNMTs) have crucial roles in the signal transduction/epigenetic pathways in GI regulation. In this review, we discuss various enzyme targets and their functional mechanisms responsible for the regulatory processes of GI malignancies. We also discuss the epigenetic therapeutic targets that are mainly facilitated by DNMT and HDAC inhibitors, which have functional consequences and clinical outcomes for GI malignancies. Our review also highlights foundation for future research with novel epigenetic biomarkers, therapeutic targets, and for insights into clinical interventions. Moreover, targeting the dysregulated epigenetic mechanism could assist with this by overwhelming cancer heterogeneity and promoting the reprogramming of cancer homeostasis. This potentiates efficacy and improves cytotoxicity of chemotherapeutic drugs and immune checkpoint inhibitors when used with epigenetic strategies.

Additionally, epigenetic profiling is essential for prognostic and predictive biomarkers, which can be used as a supportive aid for current diagnostic and therapeutic strategies that predict the response of the drug. However, the complexity of epigenetic molecular mechanisms reflects a substantial challenge and necessitates detailed study of the cellular environment and the array of therapeutic targets.

Highlights

• Discusses the epigenetics in GI cancers
• Explores the metastatic role(s) of epigenetics in GI cancers
• Presents epigenetics as biomarkers for the diagnosis and monitoring of GI cancers
• Epigenetics as therapeutic solutions for GI cancers

For more information or to refer a patient, call one of our Gastrointestinal Oncology Nurse Navigators: Erica Corcoran, MSN, RN, OCN, AOCNS, ONN-CG, at Call407-303-5981, or Wyntir Purtha, BSN, RN, OCN, at Call407-303-5959.

Read the article: https://www.sciencedirect.com/science/article/abs/pii/S1359644621002026