Abstract P4-09-04: Prevalence of phosphatidylinositol-3-kinase (PI3K) pathway alterations and co-alteration of other markers in breast cancer

2020 ◽  
Author(s):  
Katia Khoury ◽  
Antoinette Tan ◽  
Andrew Elliott ◽  
Joanne Xiu ◽  
Zoran Gatalica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pi3k Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

scholarly journals Prevalence of Phosphatidylinositol-3-Kinase (PI3K) Pathway Alterations and Co-alteration of Other Molecular Markers in Breast Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Katia Khoury ◽  
Antoinette R. Tan ◽  
Andrew Elliott ◽  
Joanne Xiu ◽  
Zoran Gatalica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Markers ◽  
Pi3k Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

Prognostic implications of phosphatidylinositol 3-kinase (PI3K) pathway alterations in metastatic triple-negative breast cancer (mTNBC).

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 1081-1081
Author(s):  
M. Oliveira ◽  
L. De Mattos-Arruda ◽  
G. Sánchez-Ollé ◽  
B. Graña ◽  
J. Cortes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pi3k Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Prognostic Implications ◽  
Phosphatidylinositol 3

scholarly journals Phosphatidylinositol 3-Kinase and Antiestrogen Resistance in Breast Cancer

2011 ◽  
Vol 29 (33) ◽  
pp. 4452-4461 ◽  
Author(s):  
Todd W. Miller ◽  
Justin M. Balko ◽  
Carlos L. Arteaga
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinases ◽  
De Novo ◽  
Clinical Investigation ◽  
Endocrine Resistance ◽  
Pi3k Pathway ◽  
Antiestrogen Resistance ◽  
Phosphatidylinositol 3 Kinase ◽  
Positive Breast Cancer ◽  
Phosphatidylinositol 3

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.

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
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Pi3k Pathway ◽  
Akt Pathway ◽  
Breast Cancers ◽  
Phosphatidylinositol 3 Kinase ◽  
Lower Treatment ◽  
Pomolic Acid ◽  
Lower Treatment Cost ◽  
Phosphatidylinositol 3

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.

scholarly journals Role of Phosphatidylinositol-3-Kinase Pathway in Head and Neck Squamous Cell Carcinoma

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Li Du ◽  
Jingping Shen ◽  
Andrew Weems ◽  
Shi-Long Lu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Pi3k Pathway ◽  
Neck Squamous Cell Carcinoma ◽  
Phosphatidylinositol 3 Kinase ◽  
Molecular Alterations ◽  
Future Direction ◽  
Phosphatidylinositol 3

Activation of the phosphatidylinositol-3-kinase (PI3K) pathway is one of the most frequently observed molecular alterations in many human malignancies, including head and neck squamous cell carcinoma (HNSCC). A growing body of evidence demonstrates the prime importance of the PI3K pathway at each stage of tumorigenesis, that is, tumor initiation, progression, recurrence, and metastasis. Expectedly, targeting the PI3K pathway yields some promising results in both preclinical studies and clinical trials for certain cancer patients. However, there are still many questions that need to be answered, given the complexity of this pathway and the existence of its multiple feedback loops and interactions with other signaling pathways. In this paper, we will summarize recent advances in the understanding of the PI3K pathway role in human malignancies, with an emphasis on HNSCC, and discuss the clinical applications and future direction of this field.

scholarly journals Phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog as therapeutic targets in breast cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769552 ◽  
Author(s):  
Ebubekir Dirican ◽  
Mustafa Akkiprik
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Breast Cancer Progression ◽  
Regulatory Subunit ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Kinase Pathway ◽  
Phosphatidylinositol 3

Breast cancer is the most commonly diagnosed cancer among women in Turkey and worldwide. It is considered a heterogeneous disease and has different subtypes. Moreover, breast cancer has different molecular characteristics, behaviors, and responses to treatment. Advances in the understanding of the molecular mechanisms implicated in breast cancer progression have led to the identification of many potential therapeutic gene targets, such as Breast Cancer 1/2, phosphatidylinositol 3-kinase catalytic subunit alpha, and tumor protein 53. The aim of this review is to summarize the roles of phosphatidylinositol 3-kinase regulatory subunit 1 (alpha) (alias p85α) and phosphatase and tensin homolog in breast cancer progression and the molecular mechanisms involved. Phosphatase and tensin homolog is a tumor suppressor gene and protein. Phosphatase and tensin homolog antagonizes the phosphatidylinositol 3-kinase/AKT signaling pathway that plays a key role in cell growth, differentiation, and survival. Loss of phosphatase and tensin homolog expression, detected in about 20%–30% of cases, is known to be one of the most common tumor changes leading to phosphatidylinositol 3-kinase pathway activation in breast cancer. Instead, the regulatory subunit p85α is a significant component of the phosphatidylinositol 3-kinase pathway, and it has been proposed that a reduction in p85α protein would lead to decreased negative regulation of phosphatidylinositol 3-kinase and hyperactivation of the phosphatidylinositol 3-kinase pathway. Phosphatidylinositol 3-kinase regulatory subunit 1 protein has also been reported to be a positive regulator of phosphatase and tensin homolog via the stabilization of this protein. A functional genetic alteration of phosphatidylinositol 3-kinase regulatory subunit 1 that results in reduced p85α protein expression and increased insulin receptor substrate 1 binding would lead to enhanced phosphatidylinositol 3-kinase signaling and hence cancer development. Phosphatidylinositol 3-kinase regulatory subunit 1 underexpression was observed in 61.8% of breast cancer samples. Therefore, expression/alternations of phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog genes have crucial roles for breast cancer progression. This review will summarize the biological roles of phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog in breast cancer, with an emphasis on recent findings and the potential of phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog as a therapeutic target for breast cancer therapy.

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