Critical questions in ovarian cancer research and treatment: Report of an American Association for Cancer Research Special Conference

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.

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

“…[ 147 ] So, on the onset of disease, ovarian cancer is thought to be an immunologically inert or “cold” tumor. [ 150 ] The heterogeneity in cell types is one critical question for relapse and recurrence or chemoresistance occurrence in clinic treatment. It is an urgent task to develop more predictive or more comprehensive models to mimic cellular heterogeneous cues in vivo, especially complex coculture cell models with multiple cell types, that are schematically illustrated on panel C in Figure 4.…”

“…[ 154 ] Largely due to technical limitations, the adhesion‐mediated signaling processes are still poorly characterized in ovarian cancer. [ 150 ] Based on the advances in bioengineering cell models in cancer biology, stem cell biology, and regenerative medicine, designer self‐assembling peptide hydrogels can increasingly cater to practical 3D cell‐patterning technologies in a relevantly physiological cell culture manner. [ 9a,10,33a,64,175 ] They may be manufactured to serve as bulk hydrogels, except of the microarchitecture similar to stromal ECM in vivo.…”

“…[ 212 ] The comparative molecular studies that fail to recognize the histopathological origins are no longer effective. [ 150,213 ] Novel ovarian cancer cell models are ongoing need to reflect the main scientific aspects for precise oncology remodeling in vitro, such as cancer cell behaviors, exosomes, and acquired chemoresistance, cell–cell coculture and cell–ECM interactions, and tumor spheroids formation, which elaborately recapitulate cell–cell and cell–ECM interactions in ovarian cancer development, progression, metastasis, dissemination or therapeutic recurrence and relapse. To capture the oncogenic drivers and tumor biology of HGSOC, fallopian tube‐based model systems may define the physiology and susceptibility of this epithelium to tumorous transformation.…”

Screening and Prevention for High-Grade Serous Carcinoma of the Ovary Based on Carcinogenesis—Fallopian Tube- and Ovarian-Derived Tumors and Incessant Retrograde Bleeding

“…The prevalence of ovarian cancer in the general population is relatively low (1:2500) [8], and higher prevalence was observed in women considered to be at high risk. High-risk women have cancer predisposing gene mutations (lifetime risk, 10-40%), i.e., those with BRCA1/BRCA2 mutations or those with Lynch syndrome.…”

Biomarkers and Strategies for Early Detection of Ovarian Cancer

“…Circulating tumor DNA (ctDNA) in blood and cervical secretions can be detected in 55% of early stage ovarian cancers and detects cases missed by CA125 alone in preliminary studies from Johns Hopkins. 60 Obtaining cervical material may be important as tumors >1 cm in diameter may be required to raise blood levels of ct DNA. 61 Shed tumor cells and cell-free DNA can pass through the fallopian tube and uterine cavity to the cervical os, without the significant dilution that occurs when DNA is shed from the cancer into peripheral blood.…”