High-throughput approaches for precision medicine in high-grade serous ovarian cancer

Govindarajan, Meinusha; Wohlmuth, Christoph; Waas, Matthew; Bernardini, Marcus Q.; Kislinger, Thomas

doi:10.1186/s13045-020-00971-6

Cited by 55 publications

(47 citation statements)

References 218 publications

(261 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Too many patients succumb to the aggressive behavior of OvCa tumor cells. Recent advances in improving personalized medicine in HGSOC patients via the high-throughput screening of biopsies combining genomics, proteomics, and metabolomics is a notable potential approach in future clinical decision-making to improve survival, as using these strategies may allow for targeted therapy in patients to exploit therapeutic liabilities of tumors to PARP inhibitors (e.g., olaparib) or anti-angiogenic agents (e.g., bevacizumab) (reviewed in [97]). As metformin has been shown to potentially induce sensitivity to these agents and improve patient responses in several cancers [98][99][100][101], it is possible that the drug may be utilized as an adjuvant to improve the therapeutic response in specific subsets of HGSOC patients.…”

Section: Discussionmentioning

confidence: 99%

Possible Role of Metformin as an Immune Modulator in the Tumor Microenvironment of Ovarian Cancer

Tsogas

Majerczyk

Hart

2021

IJMS

View full text Add to dashboard Cite

Growing evidence suggests that the immune component of the tumor microenvironment (TME) may be highly involved in the progression of high-grade serous ovarian cancer (HGSOC), as an immunosuppressive TME is associated with worse patient outcomes. Due to the poor prognosis of HGSOC, new therapeutic strategies targeting the TME may provide a potential path forward for preventing disease progression to improve patient survival. One such postulated approach is the repurposing of the type 2 diabetes medication, metformin, which has shown promise in reducing HGSOC tumor progression in retrospective epidemiological analyses and through numerous preclinical studies. Despite its potential utility in treating HGSOC, and that the immune TME is considered as a key factor in the disease’s progression, little data has definitively shown the ability of metformin to target this component of the TME. In this brief review, we provide a summary of the current understanding of the effects of metformin on leukocyte function in ovarian cancer and, coupled with data from other related disease states, posit the potential mechanisms by which the drug may enhance the anti-tumorigenic effects of immune cells to improve HGSOC patient survival.

show abstract

Section: Discussionmentioning

confidence: 99%

Possible Role of Metformin as an Immune Modulator in the Tumor Microenvironment of Ovarian Cancer

Tsogas

Majerczyk

Hart

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…The genetic, epigenetic and proteomic changes in tumors can be identified by local testing of tumor tissues or central testing of plasma cell-free DNA (cfDNA) by high-throughput approaches [ 292 ]. Local testing of DNA from tumor tissues can be achieved by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, whole-genome array-comparative genomic hybridization or next-generation sequencing (NGS), and exon-capture NGS [ 291 , 293 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting Akt in cancer for precision therapy

et al. 2021

View full text Add to dashboard Cite

Biomarkers-guided precision therapeutics has revolutionized the clinical development and administration of molecular-targeted anticancer agents. Tailored precision cancer therapy exhibits better response rate compared to unselective treatment. Protein kinases have critical roles in cell signaling, metabolism, proliferation, survival and migration. Aberrant activation of protein kinases is critical for tumor growth and progression. Hence, protein kinases are key targets for molecular targeted cancer therapy. The serine/threonine kinase Akt is frequently activated in various types of cancer. Activation of Akt promotes tumor progression and drug resistance. Since the first Akt inhibitor was reported in 2000, many Akt inhibitors have been developed and evaluated in either early or late stage of clinical trials, which take advantage of liquid biopsy and genomic or molecular profiling to realize personalized cancer therapy. Two inhibitors, capivasertib and ipatasertib, are being tested in phase III clinical trials for cancer therapy. Here, we highlight recent progress of Akt signaling pathway, review the up-to-date data from clinical studies of Akt inhibitors and discuss the potential biomarkers that may help personalized treatment of cancer with Akt inhibitors. In addition, we also discuss how Akt may confer the vulnerability of cancer cells to some kinds of anticancer agents.

show abstract

“…Some authors successfully utilized intrabursal implantation (IB) to establish ovarian PDXs [ 27 , 73 , 74 ]. However, since HGSOC subtype predominantly develops from the fallopian tube rather than the ovary, and due to the lack of ovarian bursa in humans [ 84 ], it seems more appropriate to consider intrabursal xenograft as heterotropic model, at least in the context of modeling the primary tumor.…”

Section: Patient-derived Xenograft Overviewmentioning

confidence: 99%

Patient-derived tumor models are attractive tools to repurpose drugs for ovarian cancer treatment: Pre-clinical updates

Cybula

Bieniasz

2022

Oncotarget

View full text Add to dashboard Cite

Despite advances in understanding of ovarian cancer biology, the progress in translation of research findings into new therapies is still slow. It is associated in part with limitations of commonly used cancer models such as cell lines and genetically engineered mouse models that lack proper representation of diversity and complexity of actual human tumors. In addition, the development of de novo anticancer drugs is a lengthy and expensive process. A promising alternative to new drug development is repurposing existing FDA-approved drugs without primary oncological purpose. These approved agents have known pharmacokinetics, pharmacodynamics, and toxicology and could be approved as anticancer drugs quicker and at lower cost. To successfully translate repurposed drugs to clinical application, an intermediate step of pre-clinical animal studies is required. To address challenges associated with reliability of tumor models for pre-clinical studies, there has been an increase in development of patient-derived xenografts (PDXs), which retain key characteristics of the original patient’s tumor, including histologic, biologic, and genetic features. The expansion and utilization of clinically and molecularly annotated PDX models derived from different ovarian cancer subtypes could substantially aid development of new therapies or rapid approval of repurposed drugs to improve treatment options for ovarian cancer patients.

show abstract

High-throughput approaches for precision medicine in high-grade serous ovarian cancer

Cited by 55 publications

References 218 publications

Possible Role of Metformin as an Immune Modulator in the Tumor Microenvironment of Ovarian Cancer

Possible Role of Metformin as an Immune Modulator in the Tumor Microenvironment of Ovarian Cancer

Targeting Akt in cancer for precision therapy

Patient-derived tumor models are attractive tools to repurpose drugs for ovarian cancer treatment: Pre-clinical updates

Contact Info

Product

Resources

About