Natural Compounds as Potential Regulators of the Phosphatidylinositol 3′ Kinase (PI3K) Pathway in Breast Cancer

2021 ◽  
Vol 11 (5) ◽  
pp. 524-538
Author(s):  
Anirban Roy ◽  
Indira Chakraborty ◽  
Aniruddha Banerji

Breast cancer is one of the most prevalent forms of cancer in women both globally and in India. Although breast cancer is characterized by different molecular subtypes, a majority of breast cancers appear to have mutations in the phosphatidylinositol 3′ kinase (PI3K)/ protein kinase B (Akt) pathway. Dysregulation of the PI3K/ Akt pathway in breast cancers plays important roles in promoting tumour growth, proliferation and invasion. Targeting PI3K mediated signalling cascades could be therefore of value for breast cancer treatment. Studies with synthetic inhibitors of the PI3K/ Akt pathway have yielded positive results but the efficacy shown by many of these inhibitors appear to be compromised by deleterious side effects. An alternative to syn-thetic inhibitors is the use of natural phytochemical compounds with anti-tumorigenic potential like apigenin, pomolic acid, resveratrol and its deriva-tives, curcumin, epigallocatechin-3 gallate and thymoquinone as potential inhibitors of PI3K/Akt signalling in breast cancer and such a strategy could lead to lesser side effects and a lower treatment cost. The current study ex-amines the importance of the PI3K pathway in breast cancer and discusses how regulation of aberrant signalling through this pathway by natural com-pounds could play an important role in breast cancer therapy.

2021 ◽  
Vol 22 (21) ◽  
pp. 11878
Author(s):  
Ajay Dhakal ◽  
Luna Acharya ◽  
Ruth O’Regan ◽  
Shipra Gandhi ◽  
Carla Falkson

Derangement of the phosphatidylinositol-3 kinase (PI3K) pathway is implicated in several subtypes of breast cancers. Mutation or upregulation of PI3K enhances cancer cells’ survival, proliferation, and ability to metastasize, making it an attractive molecular target for systemic therapy. PI3K has four isoforms, and several drugs targeting individual isoforms or pan-PI3K have been or are currently being investigated in clinical trials. However, the search for an effective PI3K inhibitor with a robust therapeutic effect and reasonable safety profile for breast cancer treatment remains elusive. This review focuses on the recently completed and ongoing clinical trials involving PI3K inhibitors as mono- or combination therapy in breast cancer. We review the salient findings of clinical trials, the therapeutic efficacy of PI3K inhibitors, and reported adverse effects leading to treatment discontinuation. Lastly, we discuss the challenges and potential opportunities associated with adopting PI3K inhibitors in the clinic.


2020 ◽  
Vol 10 ◽  
Author(s):  
Katia Khoury ◽  
Antoinette R. Tan ◽  
Andrew Elliott ◽  
Joanne Xiu ◽  
Zoran Gatalica ◽  
...  

2011 ◽  
Vol 29 (33) ◽  
pp. 4452-4461 ◽  
Author(s):  
Todd W. Miller ◽  
Justin M. Balko ◽  
Carlos L. Arteaga

Although antiestrogen therapies targeting estrogen receptor (ER) α signaling prevent disease recurrence in the majority of patients with hormone-dependent breast cancer, a significant fraction of patients exhibit de novo or acquired resistance. Currently, the only accepted mechanism linked with endocrine resistance is amplification or overexpression of the ERBB2 (human epidermal growth factor receptor 2 [HER2]) proto-oncogene. Experimental and clinical evidence suggests that hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway, the most frequently mutated pathway in breast cancer, promotes antiestrogen resistance. PI3K is a major signaling hub downstream of HER2 and other receptor tyrosine kinases. PI3K activates several molecules involved in cell-cycle progression and survival, and in ER-positive breast cancer cells, it promotes estrogen-dependent and -independent ER transcriptional activity. Preclinical tumor models of antiestrogen-resistant breast cancer often remain sensitive to estrogens and PI3K inhibition, suggesting that simultaneous targeting of the PI3K and ER pathways may be most effective. Herein, we review alterations in the PI3K pathway associated with resistance to endocrine therapy, the state of clinical development of PI3K inhibitors, and strategies for the clinical investigation of such drugs in hormone receptor–positive breast cancer.


Sign in / Sign up

Export Citation Format

Share Document