Contents lists available at ScienceDirect Seminars in Cancer Biology journal homepage: www.elsevier.com/locate/semcancer Recent nanotechnological interventions targeting PI3K/Akt/mTOR pathway: A focus on breast cancer VarRuchi Sharma a , Anil K. Sharma a, ⁎ , Vasu Punj b , Panneerselvam Priya c a Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, Haryana, India b Department of Medicine, Keck School of Medicine, University of Southern California, LA USA c Department of Electrical and Electronics Engineering, Thiruvalluvar College of Engineering and Technology, Vandavasi, 604505, Tamil Nadu, India ARTICLE INFO Keywords: PI3K/Akt/mTOR pathway Breast cancer Nanotechnological interventions Breast cancer biomarkers Deregulated genes ABSTRACT Breast cancer is the major cause of deaths in women worldwide. Detection and treatment of breast cancer at earlier stages of the disease has shown encouraging results. Modern genomic technologies facilitated several therapeutic options however the diagnosis of the disease at an advanced stage claim more deaths. Therefore more research directed towards genomics and proteomics into this area may lead to novel biomarkers thereby enhancing the survival rates in breast cancer patients. Phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was shown to be hyperactivated in most of the breast carci- nomas resulting in excessive growth, proliferation, and tumor development. Development of nanotechnology has provided many interesting avenues to target the PI3K/Akt/mTOR pathway both at the pre-clinical and clinical stages. Therefore, the current review summarizes the underlying mechanism and the importance of targeting PI3K/Akt/mTOR pathway, novel biomarkers and use of nanotechnological interventions in breast cancer. 1. Introduction Breast cancer is considered as the major cause of mortality in women worldwide [1]. One in every eight women is diagnosed with breast cancer in the United States [2]. Breast cancer is a heterogeneous disease [3] and it has been clas- sified into various classes based on the site of cancer cells or histology or molecular markers of breast cancer tissue (Fig. 1). Breast cancer is histologically classified broadly as lobular carcinoma in situ (LCIS), ductal carcinoma in situ (DCIS), and infiltrating ductal carcinoma (IDC) [4]. Similarly, there are five intrinsic or molecular subtypes of breast cancer that includes estrogen positive (ER) luminal A; estrogen or progesterone receptor (PR) positive; either HER2 positive or negative luminal B; ER, PR and HER2 negative triple negative/basal-like; only HER2-positive; HER2-enriched; ER/PR positive and HER2 negative [5,6]. Generally, non-invasive types of breast cancers are not aggressive towards surrounding tissues. On the contrary invasive breast cancer is known to be aggressive towards surrounding tissues resulting in inva- sion and destruction of the surrounding tissue which collectively results in metastasis. The metastasis process spreads malignant tumor cells to other parts of the body through the lymphatic system, and form a secondary tumor [7]. Various factors are shown to be involved in the pathogenesis of breast cancer including genetic factors, gender, race, family history, and personal health history [8]. Similarly, certain environmental and lifestyle factors such as poor diet, alcohol consumption, and radiation exposure [9] can also contribute to breast cancer induction and pro- gression (Fig. 2). 1.1. Symptoms of breast cancer Breast cancer starts with a breast lump that changes in the size, shape, and appearance leading to changes in the breast skin, such as the development of dimpling,flaking in the pigmented area of skin sur- rounding the nipple [10]. The acute and chronic symptoms of breast cancer comprise of weight gain, muscle mass loss, fatigue, cardiotoxi- city, cachexia, hormone alterations, bone loss, and adverse psycholo- gical effects [11]. 1.2. Treatment options Treatment options include 1. Surgery: The elimination of the tumor along with some neighboring healthy tissue through surgery is the most widely adopted treatment of malignant breast cancer [12]. 2. Radiation Therapy: It employs the use of high-energy x-rays or other particles to destroy cancer cells. A variation of radiotherapy is brachytherapy that https://doi.org/10.1016/j.semcancer.2019.08.005 Received 24 March 2019; Received in revised form 18 July 2019; Accepted 5 August 2019 ⁎ Corresponding author. E-mail address: anibiotech18@gmail.com (A.K. Sharma). Seminars in Cancer Biology xxx (xxxx) xxx–xxx 1044-579X/ © 2019 Elsevier Ltd. All rights reserved. Please cite this article as: VarRuchi Sharma, et al., Seminars in Cancer Biology, https://doi.org/10.1016/j.semcancer.2019.08.005