EGFR/HER-Targeted Therapeutics In Ovarian Cancer

Wilken, Jason A.; Badri, T.; Cross, Sarah; Raji, R; Santin, Alessandro D.; Schwartz, Peter E.; Branscum, Adam J.; Baron, Andre T.; Sakhitab, Adam I; Maihle, Nita J.

doi:10.4155/fmc.12.11

Cited by 53 publications

(33 citation statements)

References 246 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regarding, serous-like EC and serous OvCa treatment can be benefited from common targeted therapies. Indeed, there have been clinical trials utilizing EGFR and HER2 amplification in these two cancer types (Wilken et al, 2012;Makker et al, 2017). Based on our analysis, we can also propose that the frequent mutation of PIK3CA (Fig.…”

Section: Implications For Targeted Therapy Developmentsupporting

confidence: 55%

A multiomics comparison between endometrial cancer and serous ovarian cancer

Zhong

Chen

Qiu

et al. 2019

PeerJ

View full text Add to dashboard Cite

Background Endometrial carcinoma (EC) and serous ovarian carcinoma (OvCa) are both among the common cancer types in women. EC can be divided into two subtypes, endometroid EC and serous-like EC, with distinct histological characterizations and molecular phenotypes. There is an increasing awareness that serous-like EC resembles serous OvCa in genetic landscape, but a clear relationship between them is still lacking. Methods Here, we took advantage of the large-scale molecular profiling of The Cancer Genome Atlas(TCGA) to compare the two EC subtypes and serous OvCa. We used bioinformatics data analytic methods to systematically examine the somatic mutation (SM) and copy number alteration (SCNA), gene expression, pathway activities, survival gene signatures and immune infiltration. Based on these quantifiable molecular characterizations, we asked whether serous-like EC should be grouped more closely to serous OvCa, based on the context of being serous-like; or if should be grouped more closely to endometroid EC, based on the same organ origin. Results We found that although serous-like EC and serous OvCa share some common genotypes, including mutation and copy number alteration, they differ in molecular phenotypes such as gene expression and signaling pathway activity. Moreover, no shared prognostic gene signature was found, indicating that they use unique genes governing tumor progression. Finally, although the endometrioid EC and serous OvCa are both highly immune infiltrated, the immune cell composition in serous OvCa is mostly immune suppressive, whereas endometrioid EC has a higher level of cytotoxic immune cells. Overall, our genetic aberration and molecular phenotype characterizations indicated that serous-like EC and serous OvCa cannot be simply treated as a simple “serous” cancer type. In particular, additional attention should be paid to their unique gene activities and tumor microenvironments for novel targeted therapy development.

show abstract

Section: Implications For Targeted Therapy Developmentsupporting

confidence: 55%

A multiomics comparison between endometrial cancer and serous ovarian cancer

Zhong

Chen

Qiu

et al. 2019

PeerJ

View full text Add to dashboard Cite

show abstract

“…Lapatinib is able to inhibit p95-HER2 phosphorylation and as a result reduce growth of HER2 driven malignancies (114). Pan-HER TKIs which inhibit epidermal growth factor family receptors and their downstream pathways have also proved beneficial in solid tumor clinical trials (115). Also new in therapeutic approaches for solid tumors is the targeting of heat shock protein 90 (hsp90) molecular chaperone.…”

Section: Immunotherapymentioning

confidence: 99%

HER2 Expression Beyond Breast Cancer: Therapeutic Implications for Gynecologic Malignancies

2013

View full text Add to dashboard Cite

HER2 or ErbB2 is a member of the epidermal growth factor family and is overexpressed in subsets of breast, ovarian, gastric, colorectal, pancreatic and endometrial cancers. HER2 regulates signaling through several pathways (Ras/Raf/mitogen-activated protein kinase and phosphatidylinositol-3 kinase/protein kinase-B/mammalian target of rapamycin pathways) associated with cell survival and proliferation. HER2 overexpressed and/or gene amplified tumors are generally regarded as biologically aggressive neoplasms. In breast, cervical, endometrial and ovarian cancer, there have been several studies linking the amplification of the c-erbB2 gene with chemo-resistance and overall poor survival. Tyrosine kinase inhibitors and immunotherapy with monoclonal antibodies targeting HER2 holds promise for patients harboring these aggressive neoplasms. Trastuzumab combined with cytotoxic chemotherapy agents or conjugated with radioactive isotopes is currently being investigated in clinical trials of several tumor types.

show abstract

“…One of the alterations in high-grade malignant ovarian cancer is overexpression of the epidermal growth factor receptor (EGFR) 24, 25. EGFR inhibitors are potentially useful therapeutic agents in patients with advanced or recurrent ovarian cancers 26-28. However, clinical trials have been disappointing.…”

Section: Introductionmentioning

confidence: 99%

Aspirin Blocks EGF-stimulated Cell Viability in a COX-1 Dependent Manner in Ovarian Cancer Cells

Cho¹,

Kabir²,

Dong³

et al. 2013

J. Cancer

View full text Add to dashboard Cite

Objective: Although aspirin has been associated with a reduction of the risk of cancer when used as a nonsteroidal anti-inflammatory drug, its use to reduce the risk of ovarian cancer is controversial. Ovarian cancer cells usually express high levels of cyclooxygenase-1 (COX)-1. Because aspirin is a rather selective inhibitor of COX-1, the ability of aspirin to reduce the risk of ovarian cancer may be dependent on the level of COX-1 expression in those cells. Furthermore, epidermal growth factor receptor (EGFR) is frequently overexpressed in the malignant phenotype of ovarian cancer leading to increased cell proliferation and survival. Here we investigated if aspirin attenuates EGFR-activated ovarian cancer cell growth in a COX-1 dependent manner.Methods: Cell viability assays and Western blot analyses were used to determine the effect of aspirin on EGF-stimulated cell proliferation. Gene silencing and gene expression techniques were employed to knockdown or to express COX-1, respectively.Results: Aspirin inhibited cell viability induced by EGF in a dose dependent manner in COX-1 positive ovarian cancer cells. On the other hand, aspirin had no effect on cell viability in COX-1 negative ovarian cancer cells. In particular, aspirin decreased phosphorylated Akt and Erk activated by EGF. COX-1 silencing in COX-1 positive cells attenuated the inhibitory effect of aspirin on EGF-stimulated cell viability. Furthermore, we developed a COX-1 expressing cell line (SKCOX-1) by stably transfecting COX-1 expression vector into COX-1 negative SKOV-3 cells. SKCOX-1 cells were more responsive to aspirin when compared to cells transfected with empty vector, and decreased EGF-activated Akt and Erk as well as cell viability.Conclusions: Taken together, aspirin inhibits viability of ovarian cancer cells by blocking phosphorylation of Akt and Erk activated by EGF. Thus it may potentiate the therapeutic efficacy of drugs used to treat COX-1 positive ovarian cancer subsets.

show abstract

EGFR/HER-Targeted Therapeutics In Ovarian Cancer

Cited by 53 publications

References 246 publications

A multiomics comparison between endometrial cancer and serous ovarian cancer

A multiomics comparison between endometrial cancer and serous ovarian cancer

HER2 Expression Beyond Breast Cancer: Therapeutic Implications for Gynecologic Malignancies

Aspirin Blocks EGF-stimulated Cell Viability in a COX-1 Dependent Manner in Ovarian Cancer Cells

Contact Info

Product

Resources

About