Molecular Alterations in Metastatic Ovarian Cancer From Gastrointestinal Cancer

Abstract

Reports indicate that most metastatic ovarian cancer (MOC) originates from gastrointestinal cancer (GIC). Notably, GICs metastasize to the ovary frequently via 3 main routes including hematogenous spread, lymphogenous spread, and transcoelomic spread. Nonetheless, the mechanism of the progression remains unknown, and only a handful of literature exists on the molecular alteration implicated in MOC from GIC. This work collected existing evidence and literature on the vital molecules of the metastatic pathway and systematically analyzed them geared toward exploring the mechanism of the metastatic pathway of MOC. Further, this review described dominating molecular alteration in the metastatic process from cancer cells detaching away from lesions to arrive at the ovary, including factors for regulating signaling pathways in epithelial-interstitial transformation, invading, and surviving in the circulatory system or abdominal cavity. We interrogated the basis of the ovary as a distant metastatic site. This article provides new insights into the metastatic pathway and generates novel therapeutic targets for effective treatment and satisfactory outcomes in GIC patients.

PAUF as a Target for Treatment of High PAUF-Expressing Ovarian Cancer

“…Although previous in vitro studies have suggested dose-dependent effects of PAUF and anti-PAUF treatments on cell signaling activations (Park et al, 2011;Kim et al, 2013) and anti-tumor effects , respectively, it is necessary to explore dose-response of anti-PAUF against ovarian cancer in future studies. 2) A recent bioinformatic study suggests that the OVCAR-5 cancer cell line may be a metastatic ovarian cancer of upper gastrointestinal origin (Blayney et al, 2016), however, even if our findings may not best represent primary ovarian cancer, they remain highly relevant in ovarian cancer settings, because clinically, up to 20% ovarian cancers are originated from other organs (mainly from the gastrointestinal system) and show poorer prognosis (Chen et al, 2020). Whether cancers metastasized to ovary tend to express higher level of PAUF and thus benefit more from anti-PAUF treatment than primary ovarian cancer are indeed worth of further investigation.…”

Spheroid Formation and Peritoneal Metastasis in Ovarian Cancer: The Role of Stromal and Immune Components

“…After that, the most common metastatic sites are the omentum, the parietal and visceral peritoneum, as well adjacent organs via direct implantation [ 10 , 36 ]. The current scenario of intraperitoneal dissemination in OC includes tumor cell proliferation and epithelial-mesenchymal transition (EMT), the latter of which results in tumor cell migration, and, conversely, mesenchymal epithelial transition (MET), which forces the colonization of tumor cells with the formation of peritoneal implants [ 5 , 15 , 37 , 38 ].…”

Romic

“…54,55 In addition to decreased sexual function, development of osteoporosis, increased risk of cardiac events, and dementia may occur. [56][57][58] Furthermore, it has been reported that ovary removal in women below the age of 45 appears to have an increased mortality risk compared to those above this age. 57 Many negative consequences can, however, largely be prevented by the use of hormone replacement therapy (HRT), which is advised in these specific situations.…”

“…Ovarian involvement in these patients is estimated to be <1%. 55,56 The high proportion of OM within the young population stresses the need for increased awareness in the interpretation of a newly found ovarian mass on diagnostic imaging tests, especially in case of a previous history of colorectal cancer. 57 It is possible that an OM is initially misdiagnosed and surgery for a presumed primary ovarian malignancy is performed.…”

“…15,[17][18][19][20]22,[49][50][51][52][53] Other disciplines, such as gynecology and urology, offer or routinely perform prophylactic resection of the ovaries during abdominal surgery (for endometrial and muscle-invasive bladder cancers, respectively). [54][55][56] In addition, in CRC patients, the potential prevention of ovarian malignancies, which impact disease-free and overall survival, stresses the need for 'shared decision making' regarding prophylactic surgery to improve patient satisfaction. 57 Although the meta-analysis from Thompson et al 58 did not observe a superior oncologic outcome for prophylactic oophorectomy in CRC patients, no additional risk for post-operative complications or death was found.…”