Targeting the PI3K/AKT/mTOR pathway: potential for lung cancer treatment

Cheng, Haiying; Shcherba, Marina; Pendurti, Gopichand; Liang, Yuanxin; Piperdi, Bilal; Pérez-Soler, Román

doi:10.2217/lmt.13.72

Cited by 123 publications

(106 citation statements)

References 75 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…Our study reports a significant correlation between KDR and PTEN gene mutations which suggests their associated role in development of colon cancer. However, this is in contrast to one study conducted in Small cell lung cancer patients in which PI3K/AKT/ mTOR pathway status did not correlate with KDR gene [14]. This difference might be present due to different cancer groups and the small number of patients studied.…”

Section: Discussioncontrasting

confidence: 97%

“…Overall, this can mean that the KDR mutation leads to high expression of KDR protein. In addition, KDR gene mutation has been previously reported to play a therapeutic role using Regorafenib in metastatic colon cancer [14] as well as in Nonsmall cell lung cancer [27]. On the contrary, it has also been reported to occur as an adverse effect of Ramucirumab therapy [28] and may lead to side effects when used with FGFR inhibitors for treatment.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

KDR Mutation: A High-Frequency Rare Mutation and its Correlation with other Somatic Mutations in Indian Colorectal Cancer Patients

Jauhri¹,

Gupta²,

Shokeen³

et al. 2017

Next Generat Sequenc & Applic

View full text Add to dashboard Cite

Aim: This study aims to find out the frequency of KDR mutation in colorectal cancer patients and if any correlation exists between KDR mutation and demographical features or with other common and uncommon gene mutations occurring in colon cancer.Methods: FFPE samples of 112 patients were analyzed using next generation sequencing.Results: KDR gene was found to be mutated most frequently (19.6%) as compared to other uncommon gene mutations occurring among patients. 21/22 patients had the p.Q472H type of KDR mutation. It was significantly associated with mutations in PTEN (p=0.003), KRAS (p=0.026), APC (p=0.033), EGFR (p=0.036), NOTCH1 (p=0.029) and ERBB4 (p=0.008) mutations. More number of males (22.06%) harbored KDR mutations than the number of females (15.9%). A higher number of KDR mutations in Stage III (31%) as compared to other stages -I-II (19.23%) and IV (7.31%) was reported. KDR mutations were found to be in greater number in patients with lymph node metastasis (27.3%) as compared to liver metastasis (8%). However, a statistically significant association of any clinical parameter was not found. Conclusion:Our results suggest that although KDR is a rare somatic mutation in CRC, it plays a pivotal role in the development of colon cancer via angiogenesis pathway.

show abstract

Section: Discussioncontrasting

confidence: 97%

Section: Discussionmentioning

confidence: 99%

KDR Mutation: A High-Frequency Rare Mutation and its Correlation with other Somatic Mutations in Indian Colorectal Cancer Patients

Jauhri¹,

Gupta²,

Shokeen³

et al. 2017

Next Generat Sequenc & Applic

View full text Add to dashboard Cite

show abstract

“…Along with the downstream targets AKT and mTOR, PI3K is plays a central role for various physiological processes, such as cell growth, cell motility, cell survival, proliferation, differentiation, as well as in the progression of malignant disease [27]. The PI3K/Akt/mTOR pathway is known to be involved in human LC [28-30], however the finer mechanisms through by which ERS and the PI3K/Akt/mTOR pathway collaborate in mutant p53 LC are still under investigation. The central objective of this study was to explore the effects of ERS on autophagy, apoptosis and chemotherapy resistance in mutant p53 LC cells through its regulation of the PI3K/Akt/mTOR signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Gan

Zhou

Zhong

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. Methods: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53). Results: Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected. Conclusion: The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.

show abstract

“…Despite recent advances in surgery, radiation and medical treatments, the 5-year survival rate of patient with NSCLC remains one of the lowest among all major human cancers [2]. Recently, advances in molecular biology have led to an increased knowledge of the mechanisms underlying NSCLC development, especially in the PI3K/AKT signaling pathway [3,4]. The PI3K signaling pathway plays essential roles in cancer cell proliferation, survival, metabolism, motility and invasion.…”

Section: Introductionmentioning

confidence: 99%

CCR9–CCL25 interaction suppresses apoptosis of lung cancer cells by activating the PI3K/Akt pathway

Wang

Zhong

et al. 2015

Med Oncol

View full text Add to dashboard Cite

CC chemokine receptor-9 (CCR9) is highly expressed in non-small cell lung cancer (NSCLC) tissues and cell lines. However, the biological functions and the signals elicited by the interaction between CCR9 and its natural ligand CCL25 in NSCLC are unknown. Here, we selectively depleted CCR9 and inhibited CCR9-CCL25 interaction in NSCLC cells using small recombinant lentivirus-mediated miRNA, and investigated the tumorigenic effects in vitro and in vivo. Compromised CCR9-CCL25 interaction promoted apoptosis in NSCLC cells by activating phosphoinositide 3-kinase (PI3K)/Akt in vitro. In addition, we showed that CCR9-CCL25 interaction mediated the activation of the PI3K/Akt pathway in NSCLC cells, resulting in the up-regulation of anti-apoptotic proteins, as well as the down-regulation of apoptotic proteins in a PI3K-/Akt-dependent manner. These CCR9-CCL25-mediated effects were abrogated in the presence of a PI3K inhibitor (wortmannin 10 nM) or by inhibiting the CCR9-CCL25 interaction through CCR9 silencing, which also suggested that the biological function of CCR9-CCL25 was mainly regulated by PI3K. In vivo studies also demonstrated a significantly lower tumor burden in mice receiving CCR9-silence cells than those in mice receiving control cells. Together, these data suggested that CCR9-CCL25 interaction induced tumorigenesis of NSCLC cells and that this induction might be accomplished through the activation of the PI3K/Akt pathway. These findings may lead to a better understanding of the biological effects of CCR9-CCL25 interaction and provide clues for identifying novel therapeutic and preventive molecular markers for NSCLC.

show abstract

Targeting the PI3K/AKT/mTOR pathway: potential for lung cancer treatment

Cited by 123 publications

References 75 publications

KDR Mutation: A High-Frequency Rare Mutation and its Correlation with other Somatic Mutations in Indian Colorectal Cancer Patients

KDR Mutation: A High-Frequency Rare Mutation and its Correlation with other Somatic Mutations in Indian Colorectal Cancer Patients

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

CCR9–CCL25 interaction suppresses apoptosis of lung cancer cells by activating the PI3K/Akt pathway

Contact Info

Product

Resources

About