Abstract
Substantial progress has been made in understanding ovarian cancer at the molecular and cellular level. Significant improvement in 5-year survival has been achieved through cytoreductive surgery, combination platinum-based chemotherapy, and more effective treatment of recurrent cancer, and there are now more than 280,000 ovarian cancer survivors in the United States. Despite these advances, long-term survival in late-stage disease has improved little over the last 4 decades. Poor outcomes relate, in part, to late stage at initial diagnosis, intrinsic drug resistance, and the persistence of dormant drug-resistant cancer cells after primary surgery and chemotherapy. Our ability to accelerate progress in the clinic will depend on the ability to answer several critical questions regarding this disease. To assess current answers, an American Association for Cancer Research Special Conference on “Critical Questions in Ovarian Cancer Research and Treatment” was held in Pittsburgh, Pennsylvania, on October 1-3, 2017. Although clinical, translational, and basic investigators conducted much of the discussion, advocates participated in the meeting, and many presentations were directly relevant to patient care, including treatment with poly adenosine diphosphate ribose polymerase (PARP) inhibitors, attempts to improve immunotherapy by overcoming the immune suppressive effects of the microenvironment, and a better understanding of the heterogeneity of the disease.
Original language | English (US) |
---|---|
Pages (from-to) | 1963-1972 |
Number of pages | 10 |
Journal | Cancer |
Volume | 125 |
Issue number | 12 |
DOIs |
|
State | Published - Jun 15 2019 |
Externally published | Yes |
Keywords
- PARP inhibitors
- drug resistance
- early detection
- heterogeneity
- immunotherapy
- metabolism
- microenvironment
- ovarian cancer
- prevention
ASJC Scopus subject areas
- Oncology
- Cancer Research
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Critical questions in ovarian cancer research and treatment : Report of an American Association for Cancer Research Special Conference. / Bast, Robert C.; Matulonis, Ursula A.; Sood, Anil K. et al.
In: Cancer, Vol. 125, No. 12, 15.06.2019, p. 1963-1972.Research output: Contribution to journal › Comment/debate › peer-review
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TY - JOUR
T1 - Critical questions in ovarian cancer research and treatment
T2 - Report of an American Association for Cancer Research Special Conference
AU - Bast, Robert C.
AU - Matulonis, Ursula A.
AU - Sood, Anil K.
AU - Ahmed, Ahmed A.
AU - Amobi, Adaobi E.
AU - Balkwill, Frances R.
AU - Wielgos-Bonvallet, Monicka
AU - Bowtell, David D.L.
AU - Brenton, James D.
AU - Brugge, Joan S.
AU - Coleman, Robert L.
AU - Draetta, Giulio F.
AU - Doberstein, Kai
AU - Drapkin, Ronny I.
AU - Eckert, Mark A.
AU - Edwards, Robert P.
AU - Elias, Kevin M.
AU - Ennis, Darren
AU - Futreal, Andrew
AU - Gershenson, David M.
AU - Greenberg, Roger A.
AU - Huntsman, David G.
AU - Ji, Jennifer Xiao Ye
AU - Kohn, Elise C.
AU - Iavarone, Claudia
AU - Lengyel, Ernst R.
AU - Levine, Douglas A.
AU - Lord, Christopher J.
AU - Lu, Zhen
AU - Mills, Gordon B.
AU - Modugno, Francesmary
AU - Nelson, Brad H.
AU - Odunsi, Kunle
AU - Pilsworth, Jessica A.
AU - Rottapel, Robert K.
AU - Powell, Daniel J.
AU - Shen, Li
AU - Shih, Ie Ming
AU - Spriggs, David R.
AU - Walton, Josephine
AU - Zhang, Kaiyang
AU - Zhang, Rugang
AU - Zou, Lee
N1 - Funding Information: Robert C. Bast, Jr, is supported by National Cancer Institute grants P50 CA083639, P50 CA217685, and U01 CA200462, Cancer Prevention and Research Institute of Texas RP101382 and RP160145, and the National Foundation of Cancer Research. Ursula A. Matulonis is supported by the Breast Cancer Research Foundation. Anil K. Sood is supported by National Cancer Institute grant P50 CA217685 and the American Cancer Society Research Professor Award. Robert L. Coleman is supported by Cancer Prevention Research Institute of Texas grants RP210214 and RP160145. David G. Huntsman is supported by National Cancer Institute grant R01 CA19567001. Elise C. Kohn is supported by the Cancer Therapy Evaluation Program of the National Cancer Institute. Gordon B. Mills is supported by National Cancer Institute grant P50 CA217685, the Ovarian Cancer Research Foundation, the Prospect Creek Foundation, and the Adelson Medical Research Foundation. Francesmary Modugno is supported by the University School of Medicine Dean’s Faculty Advancement Fund. Rugang Zhang is supported by National Cancer Institute grants R01 CA163377 and R01 CA202919. Funding Information: Robert C. Bast Jr receives royalties for the discovery of CA 125 from Fujinabio Diagnostics Inc. Ursula A. Matulonis has acted as a member of the advisory boards for AstraZeneca, Myriad Genetics, Clovis, Eli Lilly, Mersana, Geneos, Fuji Film, and Cerulean and as a paid consultant for Merck, 2X Oncology, and Immunogen for work performed outside of the current study. Anil K. Sood has acted as a member of the scientific advisory board for Kiyatec, has received a grant from M-Trap, and is a shareholder in Biopath for work performed outside of the current study. Ahmed A. Ahmed has a patent pending for biomarkers for the early diagnosis of ovarian cancer. Monicka Wielgos-Bonvallet has received a grant from the National Center for Advancing Translational Sciences of the National Institutes of Health for work performed as part of the current study. James D. Brenton has acted as a cofounder and consultant for Inivata Ltd, has received funding to University of Cambridge for academic research collaboration grants from Aprea, has received nonfinancial support from Clovis Oncology, and has received personal fees from Bayer and AstraZeneca that were paid to the University of Cambridge for work performed outside of the current study. Joan S. Brugge has received honorarium for acting as a member of the scientific advisory board from Agios Pharmaceuticals, has received honorarium for acting as a member of the scientific advisory board from and holds stock options in Effector Pharmaceuticals, and has received grants from Roche Pharmaceuticals for work performed outside of the current study. Robert L. Coleman has received grants from the National Institutes of Health (2P50 CA109298 and P30CA016672), Gateway Foundation, and VFounation for work performed as part of the current study and has received grants from and acted as a paid consultant for AstraZeneca; has received grants from Merck; has acted as a paid consultant for Tesaro and Medivation; has received grants from and acted as a paid consultant for Clovis; has acted as a paid consultant for Gamamab; has received grants from and acted as a paid consultant for Genmab, Roche/Genentech, and Janssen; and has acted as a paid consultant for Agenus, Regeneron, and OncoQuest for work performed outside of the current study. Giulio F. Draetta reports personal fees from and stock ownership in Karyopharm Therapeutics and Metabomed, personal fees from Blueprint Medicines and Taiho Pharmaceuticals, personal fees from and stock ownership in BiovelocITA, personal fees from Helsinn Ventures, and personal fees from and stock ownership in Forma Therapeutics and Orionis Biosciences and Nurix Inc for work performed outside of the current study. Ronny I. Drapkin has acted as a member of the scientific advisory board for Repare Therapeutics, as an ad hoc advisor for nVision Medical, and as a member of the scientific advisory board for Pear Tree Pharmaceuticals and Siamab Therapeutics for work performed outside of the current study. Mark A. Eckert has a patent for droplet microfluidics for single cell analyses with royalties paid and a patent for engineered stem cell therapies for cancer with royalties paid. Kevin M. Elias has received grants from NICHD Reproductive Scientist Development Program (K12HD000849), the Robert and Deborah First Family Fund, the Honorable Tina Brozman Foundation, the Minnesota Ovarian Cancer Alliance, and the Saltonstall Foundation for work performed as part of the current study and has a patent WO2018129535A1 pending relating to the use of circulating microRNAs for the diagnosis of ovarian cancer. David M. Gershenson reports an equity interest in Biogen Inc, Johnson & Johnson, and Celgene, and has acted as a member of the advisory board for Clovis Oncology for work performed outside of the current study. Ernst R. Lengyel has a patent CT 45 in cancer pending and a patent FABP4 in ovarian cancer issued. Christopher J. Lord reports grants from AstraZeneca, Merck KGaA, and Artios for work performed as part of the current study; has acted as member of the scientific advisory board for AstraZeneca, Merck KGaA, Artios, and SunPharma; has acted as a paid consultant for GLG; has acted as member of the scientific advisory board for Vertex; has acted as a paid consultant for and owns stock in Tango; and has acted as a paid consultant for OnoPharma for work performed outside of the current study. In addition, Dr. Lord is a named inventor on patents describing the use of DNA repair inhibitors and stands to gain from the development as part of the ICR “Rewards to Inventors” scheme. Gordon B. Mills has received grants from the Susan G. Komen Breast Cancer Foundation, Ovarian Cancer Research Foundation, Breast Cancer Research Foundation, Adelson Medical Research Foundation, and Pfizer Pharmaceuticals; has received grants and personal fees from and acted as a member of the scientific advisory board for AstraZeneca; has acted as a paid consultant/member of the scientific advisory board for and has stock/options/financial in Catena Pharmaceuticals; has acted as a paid consultant/member of the scientific advisory board for and received grants from Critical Outcome Technologies; has acted as a paid consultant/member of the scientific advisory board for, has stock options in, and has received sponsored research from ImmunoMET; has acted as a paid consultant/member of the scientific advisory board for and has received sponsored research from Ionis; has acted as a paid consultant/member of the scientific advisory board for and has stock/options/financial in Signalchem Lifesciences; has acted as a paid consultant/member of the scientific advisory board for Symphogen; has acted as a paid consultant/member of the scientific advisory board for and has received sponsored research from Takeda/Millenium Pharmaceuticals; has acted as a paid consultant/member of the scientific advisory board for and has stock options in Tarveda; has stock options in Spindletop Ventures; and has received sponsored research Karus Therapeutics, Nanostring, and Prospect Creek Foundation for work performed outside of the current study. In addition, Dr. Mills has a patent HRD Assay to Myriad Genetics licensed to Myriad Genetics, and a patent DSP patent to Nanostring licensed to Nanostring. Brad H. Nelson has received personal fees from Merck, SymVivo, ImmunoVaccine, and Qu Biologics and a research grant and in-kind research funding grants from Zymeworks for work performed outside of the current study. Daniel J. Powell Jr has a patent US20160215262A1 issued. David R. Spriggs has received a grant from the National Cancer Institute (1 P01 CA190174) for work performed as part of the current study. In addition, Dr. Spriggs has a patent for MUC16 directed antibodies issued to MSK, licensed to Juno Therapeutics. The other authors made no disclosures. Publisher Copyright: © 2019 American Cancer Society
PY - 2019/6/15
Y1 - 2019/6/15
N2 - Substantial progress has been made in understanding ovarian cancer at the molecular and cellular level. Significant improvement in 5-year survival has been achieved through cytoreductive surgery, combination platinum-based chemotherapy, and more effective treatment of recurrent cancer, and there are now more than 280,000 ovarian cancer survivors in the United States. Despite these advances, long-term survival in late-stage disease has improved little over the last 4 decades. Poor outcomes relate, in part, to late stage at initial diagnosis, intrinsic drug resistance, and the persistence of dormant drug-resistant cancer cells after primary surgery and chemotherapy. Our ability to accelerate progress in the clinic will depend on the ability to answer several critical questions regarding this disease. To assess current answers, an American Association for Cancer Research Special Conference on “Critical Questions in Ovarian Cancer Research and Treatment” was held in Pittsburgh, Pennsylvania, on October 1-3, 2017. Although clinical, translational, and basic investigators conducted much of the discussion, advocates participated in the meeting, and many presentations were directly relevant to patient care, including treatment with poly adenosine diphosphate ribose polymerase (PARP) inhibitors, attempts to improve immunotherapy by overcoming the immune suppressive effects of the microenvironment, and a better understanding of the heterogeneity of the disease.
AB - Substantial progress has been made in understanding ovarian cancer at the molecular and cellular level. Significant improvement in 5-year survival has been achieved through cytoreductive surgery, combination platinum-based chemotherapy, and more effective treatment of recurrent cancer, and there are now more than 280,000 ovarian cancer survivors in the United States. Despite these advances, long-term survival in late-stage disease has improved little over the last 4 decades. Poor outcomes relate, in part, to late stage at initial diagnosis, intrinsic drug resistance, and the persistence of dormant drug-resistant cancer cells after primary surgery and chemotherapy. Our ability to accelerate progress in the clinic will depend on the ability to answer several critical questions regarding this disease. To assess current answers, an American Association for Cancer Research Special Conference on “Critical Questions in Ovarian Cancer Research and Treatment” was held in Pittsburgh, Pennsylvania, on October 1-3, 2017. Although clinical, translational, and basic investigators conducted much of the discussion, advocates participated in the meeting, and many presentations were directly relevant to patient care, including treatment with poly adenosine diphosphate ribose polymerase (PARP) inhibitors, attempts to improve immunotherapy by overcoming the immune suppressive effects of the microenvironment, and a better understanding of the heterogeneity of the disease.
KW - PARP inhibitors
KW - drug resistance
KW - early detection
KW - heterogeneity
KW - immunotherapy
KW - metabolism
KW - microenvironment
KW - ovarian cancer
KW - prevention
UR - http://www.scopus.com/inward/record.url?scp=85062528733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062528733&partnerID=8YFLogxK
U2 - 10.1002/cncr.32004
DO - 10.1002/cncr.32004
M3 - Comment/debate
C2 - 30835824
AN - SCOPUS:85062528733
SN - 0008-543X
VL - 125
SP - 1963
EP - 1972
JO - Cancer
JF - Cancer
IS - 12
ER -