• 33259 Citations
  • 92 h-Index
1976 …2020
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Personal profile

Research interests

As an oncologist and pharmacologist, my overall research goal is to improve the therapy of neoplastic diseases, with an emphasis on hematological malignancies that dates back to the mid-1980s and research on ovarian cancer that dates to 1994 when I moved to the Mayo Clinic.  Over the past 30 years my laboratory group has performed basic studies examining the biochemistry and biology of apoptosis, a cell death process that is triggered by a variety of anticancer treatments in susceptible cells.  We are continuing that work with an increasing emphasis on ovarian cancer. In addition, we have performed preclinical and translational studies on a variety of chemotherapeutics, including topoisomerase I poisons, gemcitabine, modulators of platinum sensitivity, and checkpoint kinase inhibitors, all of which have been investigated as potential therapeutics for ovarian cancer.  For example, our work on PARP inhibitors, which builds on studies of PARP biology that began in my laboratory in 1985, has over the past six years started to provide exciting new insight into the action of this exciting new class of agents. In particular, our studies have not only emphasized the role of alterations in particular repair pathways on sensitivity to PARP inhibitors, but also  demonstrated that PARP inhibitors sensitize homologous recombination-proficient cells to a variety of anticancer agents through several different mechanisms, including inhibition of base excision repair (sensitization to floxuridine), trapping of PARP1 on DNA to prevent DNA repair (sensitization to topotecan) and altered binding of transcription factors to promoters (sensitization to TRAIL and Fas ligand). 

As a practicing oncologist, I have tried whenever possible to use my laboratory's findings to guide the investigation of new therapies.  These efforts have led to several clinical trials, including single-agent rucaparib for platinum sensitive ovarian cancer (the ARIEL2 trial originally designed in collaboration with Elizabeth Swisher), topotecan + veliparib for platinum-resistant ovarian cancer, temsirolimus for mantle cell lymphoma, topotecan + carboplatin + veliparib for transformed myeloproliferative neoplasms, tipifarnib for relapsed T cell lymphoma, and tipifarnib + etoposide for relapsed AML.

Research interests

As an oncologist and pharmacologist, my overall research goal is to improve the therapy of neoplastic diseases, with an emphasis on hematological malignancies that dates back to the mid-1980s and research on ovarian cancer that dates to 1994 when I moved to the Mayo Clinic.  Over the past 30 years my laboratory group has performed basic studies examining the biochemistry and biology of apoptosis, a cell death process that is triggered by a variety of anticancer treatments in susceptible cells.  We are continuing that work with an increasing emphasis on ovarian cancer. In addition, we have performed preclinical and translational studies on a variety of chemotherapeutics, including topoisomerase I poisons, gemcitabine, modulators of platinum sensitivity, and checkpoint kinase inhibitors, all of which have been investigated as potential therapeutics for ovarian cancer.  For example, our work on PARP inhibitors, which builds on studies of PARP biology that began in my laboratory in 1985, has over the past six years started to provide exciting new insight into the action of this exciting new class of agents. In particular, our studies have not only emphasized the role of alterations in particular repair pathways on sensitivity to PARP inhibitors, but also  demonstrated that PARP inhibitors sensitize homologous recombination-proficient cells to a variety of anticancer agents through several different mechanisms, including inhibition of base excision repair (sensitization to floxuridine), trapping of PARP1 on DNA to prevent DNA repair (sensitization to topotecan) and altered binding of transcription factors to promoters (sensitization to TRAIL and Fas ligand). 

As a practicing oncologist, I have tried whenever possible to use my laboratory's findings to guide the investigation of new therapies.  These efforts have led to several clinical trials, including single-agent rucaparib for platinum sensitive ovarian cancer (the ARIEL2 trial originally designed in collaboration with Elizabeth Swisher), topotecan + veliparib for platinum-resistant ovarian cancer, temsirolimus for mantle cell lymphoma, topotecan + carboplatin + veliparib for transformed myeloproliferative neoplasms, tipifarnib for relapsed T cell lymphoma, and tipifarnib + etoposide for relapsed AML.

Keywords

  • RM Therapeutics. Pharmacology
  • Molecular pharmacology
  • Anticancer drug resistance
  • Apoptosis
  • Death receptor
  • Mitochondrial pathway
  • BCL2 proteins
  • Topoisomerases
  • DNA repair inhibitors
  • Signal transduction inhibitors
  • PARP inhibitors
  • Platinum compounds
  • R Medicine (General)
  • Medical oncology
  • Ovarian cancer
  • Hematology
  • Follicular lymphoma
  • Acute myeloid leukemia
  • Acute lymphoblastic leukemia

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  • 4 Similar Profiles
Apoptosis Medicine & Life Sciences
Topotecan Medicine & Life Sciences
Acute Myeloid Leukemia Medicine & Life Sciences
Neoplasms Medicine & Life Sciences
Type I DNA Topoisomerase Medicine & Life Sciences
tipifarnib Medicine & Life Sciences
irinotecan Medicine & Life Sciences
Leukemia Medicine & Life Sciences

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Projects 1985 2020

Death Domain Receptors
Ligands
Apoptosis
Cell Death
Immunotherapy
Ovarian Neoplasms
Mutation
Down-Regulation
Double-Stranded DNA Breaks
Neoplasms

Poisoning of PARP and Topoisomerase I to Treat Ovarian Cancer

Shridhar, V., Kaufmann, S. H., Cliby, W. A., Bible, K. C., Goode, E. L., Peng, K., Galanis, E., Knutson, K. L., Hartmann, L. C., Lingle, W. L., Oberg, A. L., Couch, F. J., Fields, A. P., Haluska, P. R. J., Long, H., Bell, D., Keeney, G., Lengyel, E. & Keeney, G.

National Institutes of Health

10/1/088/31/20

Project: Research project

Ovarian Neoplasms
alvocidib
Registries
Research
Translational Medical Research
Mitochondrial Membranes
bcl-2 Homologous Antagonist-Killer Protein
Noxae
Pharmaceutical Preparations
Proteins

Research Output 1976 2019

53BP1 as a potential predictor of response in PARP inhibitor-treated homologous recombination-deficient ovarian cancer

Hurley, R. M., Wahner Hendrickson, A. E., Visscher, D. W., Ansell, P., Harrell, M. I., Wagner, J. M., Negron, V., Goergen, K. M., Maurer, M. J., Oberg, A. L., Meng, X. W., Flatten, K. S., De Jonge, M. J. A., Van Herpen, C. D., Gietema, J. A., Koornstra, R. H. T., Jager, A., den Hollander, M. W., Dudley, M., Shepherd, S. P. & 2 othersSwisher, E. M. & Kaufmann, S. H., Jan 1 2019, (Accepted/In press) In : Gynecologic Oncology.

Research output: Contribution to journalArticle

Homologous Recombination
Ovarian Neoplasms
DNA End-Joining Repair
Neoplasms
Gene Deletion

Effect of CHK1 Inhibition on CPX-351 Cytotoxicity in vitro and ex vivo

Vincelette, N. D., Ding, H., Huehls, A. M., Flatten, K. S., Kelly, R. L., Kohorst, M. A., Webster, J., Hess, A. D., Pratz, K. W., Karnitz, L. M. & Kaufmann, S. H., Dec 1 2019, In : Scientific reports. 9, 1, 3617.

Research output: Contribution to journalArticle

Open Access
Acute Myeloid Leukemia
Cytarabine
Daunorubicin
G2 Phase Cell Cycle Checkpoints
In Vitro Techniques
5 Citations (Scopus)

A phase i clinical trial of the Poly(ADP-ribose) polymerase inhibitor veliparib and weekly topotecan in patients with solid tumors

Wahner Hendrickson, A. E., Menefee, M. E., Hartmann, L. C., Long, H. J., Northfelt, D. W., Reid, J. M., Boakye-Agyeman, F., Kayode, O., Flatten, K. S., Harrell, M. I., Swisher, E. M., Poirer, G. G., Satele, D., Allred, J., Lensing, J. L., Chen, A., Ji, J., Zang, Y., Erlichman, C., Haluska, P. & 1 othersKaufmann, S. H., Feb 15 2018, In : Clinical Cancer Research. 24, 4, p. 744-752 9 p.

Research output: Contribution to journalArticle

Topotecan
Clinical Trials
Neoplasms
Maximum Tolerated Dose
Mutation
tipifarnib
Farnesyltranstransferase
Epidermal Growth Factor
Protein-Tyrosine Kinases
Maximum Tolerated Dose
1 Citation (Scopus)

A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease

Litzow, M. R., Wang, X. V., Carroll, M. P., Karp, J. E., Ketterling, R. P., Zhang, Y., Kaufmann, S. H., Lazarus, H. M., Luger, S. M., Paietta, E. M., Pratz, K. W., Tun, H. W., Altman, J. K., Broun, E. R., Rybka, W. B., Rowe, J. M. & Tallman, M. S., Jan 1 2018, (Accepted/In press) In : American Journal of Hematology.

Research output: Contribution to journalArticle

alvocidib
Mitoxantrone
Cytarabine
Acute Myeloid Leukemia
Topotecan