Oncogenic Mutations in Tumorigenesis and Targeted Therapy in Breast Cancer

• Published in: Current molecular biology reports 2020, Vol.6 (3), p.116-125
• Main Authors: Kumar, Brijesh, Chand, Vaibhav, Ram, Anupama, Usmani, Darksha, Muhammad, Naoshad
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer therapies; ErbB-2 protein; Genomic instability; Human Genetics; Molecular Biology of Cell Death and Aging (N Razdan and N Muhammad; Molecular Medicine; Mutation; Patients; Progesterone; Section Editors; Therapeutic applications; Topical Collection on Molecular Biology of Cell Death and Aging; Tumorigenesis
• ISSN: 2198-6428; 2198-6428
• DOI: 10.1007/s40610-020-00136-x

Purpose of Review Breast cancer is the most frequently identified cancer and the leading cause of women death from cancer worldwide. Although, based on the molecular classification, various therapeutic interventions are available for this deadly disease. However, increasing evidence suggests existence of differential mutation patterns in various cellular pathways crucial for the regulation of tumor microenvironment, cellular plasticity, and genomic instability. Genomic instability leads to the deregulation of oncogenic signaling pathways and makes it harder to find specific target in order to apply an effective therapy. Additionally, the deregulated oncogenic pathways acquire the gain of functions which makes the tumor more resilient to the available therapeutic intervention. These oncogenic mutations are also responsible for aiding up to tumor heterogeneity. Tumor heterogeneity in turn increases the intra-tumor diversity and the existence of various clonal population complicates the tumor diagnostic which leads to therapeutic challenges. In this review, we talked about the need of further molecular stratification of breast cancer to better understand the targetable mutation pattern and to design the effective outcome of treatment. Recent Findings Tumor heterogeneity has a serious clinical consequence for the breast cancer patients. However, there are no known ways to target the tumor heterogeneity yet. Although, we think that the future is in the hand of personalized medication in order to target the tumor heterogeneity, which still has a long way to go. Current treatment choices are mostly based on the molecular classification such as status of hormone receptors estrogen receptor, progesterone receptor, and HER2 expressions. The advancement in the global sequencing devices has given great advantages in understanding the tumor heterogeneity and identification of additional mutation patterns, which are being targeted in combination with available treatments for the better outcome of the patient’s survival. Summary We summarize the clinical challenges and opportunities for better management of breast cancer patients and treatment choices. Investigating the mutational signatures and their associated mechanisms responsible for cancer could be a new evolving target and thus improve the opportunities for therapy.