TRAIL and guardian angel of genome integrity: ATM boards TRAIL blazer

Farooqı, Ammad Ahmad; Waseem, Salman; Ashraf, Mohammad; Iqbal, Muhammad; Bhatti, Shahzad

doi:10.1007/s00432-011-0996-y

Cited by 5 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, the analysis of ATM expression and activity, using immunohistochemistry approaches with specific antibodies may allow to predict the ability of DNA damaging agents to trigger ATM activation and FLIP downregulation in those tumors where TRAIL resistance has been clearly linked to FLIP proteins upregulation. Future studies will clarify whether and in which conditions ATM may represent a putative marker for the screening and the identification of those tumors which may be successfully targeted by the combination of TRAIL and DNA damage drugs (discusses also in [127]). This finding may contribute to the development of more personalized and therefore effective targeted therapies.…”

Section: Discussionmentioning

confidence: 99%

A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase

Stagni

Santini

Barilá

2012

Cancers

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCCs are genetically and phenotypically heterogeneous tumors characterized by very poor prognosis, mainly due to the lack, at present, of effective therapeutic options, as these tumors are rarely suitable for radiotherapy and often resistant to chemotherapy protocols. In the last years, agonists targeting the Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) death receptor, has been investigated as a valuable promise for cancer therapy, based on their selectivity for malignant cells and low toxicity for healthy cells. However, many cancer models display resistance to death receptor induced apoptosis, pointing to the requirement for the development of combined therapeutic approaches aimed to selectively sensitize cancer cells to TRAIL. Recently, we identified ATM kinase as a novel modulator of the ability of chemotherapeutic agents to enhance TRAIL sensitivity. Here, we review the biological determinants of HCC responsiveness to TRAIL and provide an exhaustive and updated analysis of the molecular mechanisms exploited for combined therapy in this context. The role of ATM kinase as potential novel predictive biomarker for combined therapeutic approaches based on TRAIL and chemotherapeutic drugs will be closely discussed.

show abstract

Section: Discussionmentioning

confidence: 99%

A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase

Stagni

Santini

Barilá

2012

Cancers

View full text Add to dashboard Cite

show abstract

“…Wingless (WNT) and Sonic Hedgehog (SHH) signaling cascades were shown to participate in cross talk with TRAIL pathway in prostate cancer cells [ 22 ]. Ataxia Telangiectasia Mutated protein kinase (ATM), a member of phosphatidyl-inositol 3-kinase-related kinase family, known to trigger cell death response to DNA damage, has been shown to regulate TRAIL-mediated signaling [ 23 ]. The ATM/p53 signaling axis controls the transcriptional regulation of death receptors [ 23 ].…”

Section: Trail Signaling and Mechanisms Of Tumor Resistance To Trailmentioning

confidence: 99%

Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra

Farooqı

Gadaleta

Ranieri

et al. 2016

View full text Add to dashboard Cite

Cancer is a multifaceted disease. Our deepened knowledge about genetic and biological mechanisms of cancer cells presents an opportunity to explore the inter-individual differences in the body’s ability to metabolize and respond to different nutrients. It is becoming progressively more understandable that the deregulation of several signaling pathways and the alterations in apoptotic response are some of the major determinants that underpin carcinogenesis. Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL)-mediated signaling has gained a remarkable appreciation because of its ability to selectively induce apoptosis in cancer cells leaving normal cells intact. However, technological advances have started to shed light on underlying mechanisms of resistance against TRAIL-induced apoptosis in cancer cells. The impairment of TRAIL-mediated apoptosis includes various factors ranging from the loss or down regulation of TRAIL receptors or pro-apoptotic proteins to the up regulation of anti-apoptotic proteins. Intriguingly to mention that there is an ever-increasing number of natural herbal extracts (phytometabolites), which have been explored to date for their potential action in restoring apoptosis TRAIL-mediated in cancer cells. In this review, we will highlight the progress in understanding the mechanisms opted by phenolic compounds in overcoming TRAIL resistance.

show abstract

“…It is a well established fact that TRAIL binds to two cell-death-inducing (DR4 and DR5) and two decoy (DcR1, and DcR2) receptors. Various reviews have been written highlighting role of TRAIL mediated signaling cascade in prostate cancer [1-3]. Escalating preclinical studies reveal that the TRAIL ligand can efficiently induce cancer cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

TRAIL and vitamins: opting for keys to castle of cancer proteome instead of open sesame

Farooqı

Bhatti

Ismail

2012

Cancer Cell International

Self Cite

View full text Add to dashboard Cite

Cancer is a multifaceted molecular disorder that is modulated by a combination of genetic, metabolic and signal transduction aberrations, which severely impair the normal homeostasis of cell growth and death. Accumulating findings highlight the fact that different genetic alterations, such as mutations in tumor suppressor genes, might be related to distinct and differential sensitivity to targeted therapies. It is becoming increasingly apparent that a multipronged approach that addresses genetic milieu (alterations in upstream and/or parallel pathways) eventually determines the response of individual tumors to therapy. Cancerous cells often acquire the ability to evade death by attenuating cell death pathways that normally function to eliminate damaged and harmful cells. Therefore impaired cell death nanomachinery and withdrawal of death receptors from cell surface are some of major determinants for the development of chemotherapeutic resistance encountered during treatment. It is therefore essential to emphasize underlying factors which predispose cells to refractoriness against TRAIL mediated cell death pathway and the relevant regulatory components involved. We bring to limelight the strategies to re-sensitize TRAIL resistant cells via vitamins to induce apoptosis.

show abstract

TRAIL and guardian angel of genome integrity: ATM boards TRAIL blazer

Cited by 5 publications

References 16 publications

A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase

A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase

Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra

TRAIL and vitamins: opting for keys to castle of cancer proteome instead of open sesame

Contact Info

Product

Resources

About