Induction (neoadjuvant) chemotherapy for locally advanced head and neck cancer (LAHNC) constitutes a three drug regimen consisting of a taxane, a platin, and 5-fluorouracil (TPF). TPF induction chemotherapy is effective but is associated with significant toxicity especially myelosuppression and mucositis. Overall response rates exceeding 80% and complete response (CR) rates ranging from 20 to 54% have been reported. Achieving CR correlates with good prognosis while failure to respond to induction chemotherapy predicts resistance to subsequent radiotherapy. Toward enhancing CR rates after induction therapy in LAHNC, we have initiated a trial combining the poly(ADP-ribose) polymerase inhibitor veliparib with cisplatin, 5FU and docetaxel therapy. Previously, we have shown that veliparib enhances accelerated senescence in cells and tumors treated with radiation or genotoxic therapy. Here, we intend to pursue parallel preclinical research constituting correlative studies for this trial. Thus, we intend to examine tissue culture, animal models and biopsies from treated patient tumors to understand whether accelerated senescence is a potential mediator of success in induction therapy, with or without veliparib. We also hope to identify biomarkers that indicate sensitivity to veliparib and/or induction therapy, and that indicate success of these treatments.
Head and neck cancer remains a considerable health challenge. This study is directed at improving the initial treatment of patients to increase cures. By testing whether the PARP inhibitor veliparib can enhance chemotherapy, we hope to identify a low toxicity drug that can improve outcomes without increasing side effects.
|Sánchez-Botet, Abril; Gasa, Laura; Quandt, Eva et al. (2018) The atypical cyclin CNTD2 promotes colon cancer cell proliferation and migration. Sci Rep 8:11797|
|Efimova, Elena V; Ricco, Natalia; Labay, Edwardine et al. (2018) HMG-CoA Reductase Inhibition Delays DNA Repair and Promotes Senescence After Tumor Irradiation. Mol Cancer Ther 17:407-418|
|Gasa, L; Sanchez-Botet, A; Quandt, E et al. (2017) A systematic analysis of orphan cyclins reveals CNTD2 as a new oncogenic driver in lung cancer. Sci Rep 7:10228|
|Flor, Amy C; Wolfgeher, Don; Wu, Ding et al. (2017) A signature of enhanced lipid metabolism, lipid peroxidation and aldehyde stress in therapy-induced senescence. Cell Death Discov 3:17075|
|Flor, Amy C; Kron, Stephen J (2016) Lipid-derived reactive aldehydes link oxidative stress to cell senescence. Cell Death Dis 7:e2366|
|Flor, A C; Doshi, A P; Kron, S J (2016) Modulation of therapy-induced senescence by reactive lipid aldehydes. Cell Death Discov 2:|
|Labay, Edwardine; Mauceri, Helena J; Efimova, Elena V et al. (2016) Repurposing cephalosporin antibiotics as pro-senescent radiosensitizers. Oncotarget 7:33919-33|
|Duan, Xiaopin; He, Chunbai; Kron, Stephen J et al. (2016) Nanoparticle formulations of cisplatin for cancer therapy. Wiley Interdiscip Rev Nanomed Nanobiotechnol 8:776-91|
|Skowron, K B; Pitroda, S P; Namm, J P et al. (2016) Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers. Sci Rep 6:35854|
|Efimova, Elena V; Takahashi, Satoe; Shamsi, Noumaan A et al. (2016) Linking Cancer Metabolism to DNA Repair and Accelerated Senescence. Mol Cancer Res 14:173-84|
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