The role of PARP inhibition in triple-negative breast cancer: Unraveling the wide spectrum of synthetic lethality

Papadimitriou, Marios; Mountzios, Giannis; Papadimitriou, Christos

doi:10.1016/j.ctrv.2018.04.010

Cited by 80 publications

(73 citation statements)

References 89 publications

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“…Finally, synthetic lethality has been of great interest for patients with BRCA1/2 mutations, for whom PARP inhibitors have shown promising therapeutic benefit [106, 107]. BRCA1/2 facilitate HR repair of double-strand breaks (DSB) and are functionally impaired by cancer-associated mutations.…”

Section: Pp2a Inhibitionmentioning

confidence: 99%

Targeting PP2A in cancer: Combination therapies

Mazhar¹,

Taylor²,

Sangodkar³

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

110

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The serine/threonine phosphatase PP2A regulates a vast portion of the phosphoproteome including pathways involved in apoptosis, proliferation and DNA damage response and PP2A inactivation is a vital step in malignant transformation. Many groups have explored the therapeutic venue of combining PP2A reactivation with kinase inhibition to counteract the very changes in tumor suppressors and oncogenes that lead to cancer development. Conversely, inhibition of PP2A to complement chemotherapy and radiation-induced cancer cell death is also an area of active investigation. Here we review the studies that utilize PP2A targeted agents as combination therapy in cancer. A potential role for PP2A in tumor immunity is also highlighted.

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Section: Pp2a Inhibitionmentioning

confidence: 99%

Targeting PP2A in cancer: Combination therapies

Mazhar¹,

Taylor²,

Sangodkar³

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

110

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show abstract

“…1 42 In addition to combination immune checkpoint and chemotherapy trials, PARP inhibitors are also undergoing early phase trials for the treatment of TNBC, especially when associated with homologous recombination deficiency. 43 Despite these new treatments, early data show modest improvements in survival, underscoring the need to improve therapeutic outcome for patients with TNBC. Autologous tumor cell vaccines are an antigen agnostic form of personalized immunotherapy.…”

Section: Icv Enhances Immune Signature and Biomarkers Of Icd In Humanmentioning

confidence: 99%

Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8⁺T-cell functionality

Niavarani

Lawson

Boudaud

et al. 2020

J Immunother Cancer

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“…Poly ADP ribose polymerase (PARP) inhibitors are currently the most promising agents in this group, based on the similarity of this subtype to ovarian cancers. [73][74][75][76][77] Alternative holistic approaches are being continuously sought as the World Health Organization (WHO) forecasts that approximately 80% of the global population would use one or the other form of alternative medicine in their life time. 78 In this report, we have described the application of green nanotechnology to holistic Ayurvedic medicine.…”

Section: Discussion Related To Pilot Clinical Trial Investigationsmentioning

confidence: 99%

<p>New Approaches in Breast Cancer Therapy Through Green Nanotechnology and Nano-Ayurvedic Medicine – Pre-Clinical and Pilot Human Clinical Investigations</p>

Khoobchandani

Katti

Karikachery

et al. 2020

IJN

105

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The overarching objective of this investigation was to investigate the intervention of green nanotechnology to transform the ancient holistic Ayurvedic medicine scientifically credible through reproducible formulations and rigorous pre-clinical/clinical evaluations. Methods: We provide, herein, full details: (i) on the discovery and full characterization of gold nanoparticles-based Nano Swarna Bhasma (henceforth referred to as NSB drug); (ii) In vitro anti-tumor properties of NSB drug in breast tumor cells; (iii) pre-clinical therapeutic efficacy studies of NSB drug in breast tumor bearing SCID mice through oral delivery protocols and (iv) first results of clinical translation, from mice to human breast cancer patients, through pilot human clinical trials, conducted according to the Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy (abbreviated as AYUSH) regulatory guidelines of the Government of India in metastatic breast cancer patients. Results: The preclinical in vitro and in vivo investigations, in breast tumor bearing mice, established unequivocally that the NSB Nano-Ayurvedic medicine-gold nanoparticles-based drug is highly effective in controlling the growth of breast tumors in a dose dependent fashion in vivo. These encouraging pre-clinical results prompted us to seek permission from the Indian Government's holistic medicine approval authority, AYUSH, for conducting clinical trials in human patients. Patients treated with the NSB drug capsules along with the "standard of care treatment" (Arm B) exhibited 100% clinical benefits when compared to patients in the treatment Arm A, thus indicating the tremendous clinical benefits of NSB drug in adjuvant therapy. Conclusion: We have succeeded in clinically translating, from mice to humans, in using proprietary combinations of gold nanoparticles and phytochemicals to develop the Nano-Ayurvedic drug: Nano Swarna Bhasma (NSB), through innovative green nanotechnology, for treating human metastatic breast cancer patients.

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The role of PARP inhibition in triple-negative breast cancer: Unraveling the wide spectrum of synthetic lethality

Cited by 80 publications

References 89 publications

Targeting PP2A in cancer: Combination therapies

Targeting PP2A in cancer: Combination therapies

Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8⁺T-cell functionality

<p>New Approaches in Breast Cancer Therapy Through Green Nanotechnology and Nano-Ayurvedic Medicine – Pre-Clinical and Pilot Human Clinical Investigations</p>

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The role of PARP inhibition in triple-negative breast cancer: Unraveling the wide spectrum of synthetic lethality

Cited by 80 publications

References 89 publications

Targeting PP2A in cancer: Combination therapies

Targeting PP2A in cancer: Combination therapies

Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8+T-cell functionality

<p>New Approaches in Breast Cancer Therapy Through Green Nanotechnology and Nano-Ayurvedic Medicine – Pre-Clinical and Pilot Human Clinical Investigations</p>

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Product

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About

Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8⁺T-cell functionality