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  • Open Access

    ARTICLE

    mTORC2 promotes pancreatic cancer progression and parp inhibitor resistance

    CHIWEN BU1,2, LIGANG ZHAO1, LISHAN WANG1, ZEQIAN YU1, JIAHUA ZHOU1,*

    Oncology Research, Vol.31, No.4, pp. 495-503, 2023, DOI:10.32604/or.2023.029309

    Abstract Pancreatic cancer is one of the most aggressive cancers with a median survival time of less than 5 months, and conventional chemotherapeutics are the main treatment strategy. Poly(ADP-ribose) polymerase (PARP) inhibitors have been recently approved for BRCA1/2-mutant pancreatic cancer, opening a new era for targeted therapy for this disease. However, most pancreatic cancer patients carry wild-type BRCA1/2 with resistance to PARP inhibitors. Here, we reported that mammalian target of rapamycin complex 2 (mTORC2) kinase is overexpressed in pancreatic cancer tissues and promotes pancreatic cancer cell growth and invasion. Moreover, we found that knockdown of the mTORC2 obligate subunit Rictor sensitized… More > Graphic Abstract

    mTORC2 promotes pancreatic cancer progression and parp inhibitor resistance

  • Open Access

    REVIEW

    Targeting DNA repair for cancer treatment: Lessons from PARP inhibitor trials

    DHANYA K. NAMBIAR1, DEEPALI MISHRA2, RANA P. SINGH2,3,*

    Oncology Research, Vol.31, No.4, pp. 405-421, 2023, DOI:10.32604/or.2023.028310

    Abstract Ionizing radiation is frequently used to treat solid tumors, as it causes DNA damage and kill cancer cells. However, damaged DNA is repaired involving poly-(ADP-ribose) polymerase-1 (PARP-1) causing resistance to radiation therapy. Thus, PARP-1 represents an important target in multiple cancer types, including prostate cancer. PARP is a nuclear enzyme essential for single-strand DNA breaks repair. Inhibiting PARP-1 is lethal in a wide range of cancer cells that lack the homologous recombination repair (HR) pathway. This article provides a concise and simplified overview of the development of PARP inhibitors in the laboratory and their clinical applications. We focused on the… More > Graphic Abstract

    Targeting DNA repair for cancer treatment: Lessons from PARP inhibitor trials

  • Open Access

    REVIEW

    Is autophagy induction by PARP inhibitors a target for therapeutic benefit?

    AHMED M. ELSHAZLY1,2, TUONG VI V. NGUYEN1, DAVID A. GEWIRTZ1,*

    Oncology Research, Vol.30, No.1, pp. 1-12, 2022, DOI:10.32604/or.2022.026459

    Abstract PARP inhibitors have proven to be effective in conjunction with conventional therapeutics in the treatment of various solid as well as hematologic malignancies, particularly when the tumors are deficient in DNA repair pathways. However, as the case with other chemotherapeutic agents, their effectiveness is often compromised by the development of resistance. PARP inhibitors have consistently been reported to promote autophagy, a process that maintains cellular homeostasis and acts as an energy source by the degradation and reutilization of damaged subcellular organelles and proteins. Autophagy can exhibit different functional properties, the most prominent being cytoprotective. In addition, both cytotoxic and non-protective… More >

  • Open Access

    VIEWPOINT

    Poly(ADP-ribose), adherens junctions, vinculin and the actin cytoskeleton: Current evidence, future perspectives and implications

    LAURA LAFON-HUGHES1,2,*

    BIOCELL, Vol.46, No.12, pp. 2531-2535, 2022, DOI:10.32604/biocell.2022.022713

    Abstract Poly(ADP-ribose) (PAR) is a highly negatively charged polymer. PAR is synthesized by poly(ADP-ribose)polymerases (PARPs) and is involved in the assembly and stabilization of macromolecular complexes. Here, the presence and putative roles of poly(ADP-ribosyl)ation (PARylation) associated to adherens junctions (AJ) and the actin cytoskeleton in epithelial and Schwann cells, is reviewed. The hypothesis generated by analogy, stating that PAR is associated to AJ in other cell types, is postulated. According to this hypothesis, PAR associated to puncta adherentia in chemical synapses would participate in plasticity, learning and memory. In turn, PAR associated to fascia adherens in cardiomyocytes, would affect heart beating.… More >

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