Immunologic aspect of ovarian cancer and p53 as tumor antigen

Nijman, HW; Lambeck, Annechien J. A.; Burg, SH van der; Zee, Agj van der; Daemen, Toos

doi:10.1186/1479-5876-3-34

Cited by 32 publications

(12 citation statements)

References 133 publications

(105 reference statements)

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“…Nonetheless, P53 is highly mutated in gynecological cancers ( > 90% in ovaries and 25-85% in the endometrium) being an important factor for tumorigenesis and cancer initiation (Figure 2C ) [ 92 , 152 , 154 ]. Also noteworthy, ovarian and endometrial cancers frequently overexpress P53, WT or mutant [ 154 – 156 ]. Considering the importance of P53 apoptosis pathway, it appears clear that this protein is involved in gynecological cancers response to chemotherapy.…”

Section: Chemoresistance In Gynecological Cancersmentioning

confidence: 99%

“…Many therapeutic avenues have been studied concerning P53. Another aspect to consider is the high amount of gynecological cancers overexpressing P53, making this protein an interesting target for therapy [ 154 – 156 ]. However, because of its multiple mechanisms and mutations, high levels of effectiveness are hard to achieve.…”

Section: Targeted Therapies To Overcome Chemoresistancementioning

confidence: 99%

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Chemoresistance and targeted therapies in ovarian and endometrial cancers

2016

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Gynecological cancers are known for being very aggressive at their advanced stages. Indeed, the survival rate of both ovarian and endometrial cancers is very low when diagnosed lately and the success rate of current chemotherapy regimens is not very efficient. One of the main reasons for this low success rate is the acquired chemoresistance of these cancers during their progression. The mechanisms responsible for this acquired chemoresistance are numerous, including efflux pumps, repair mechanisms, survival pathways (PI3K/AKT, MAPK, EGFR, mTOR, estrogen signaling) and tumor suppressors (P53 and Par-4). To overcome these resistances, a new type of therapy has emerged named targeted therapy. The principle of targeted therapy is simple, taking advantage of changes acquired in malignant cancer cells (receptors, proteins, mechanisms) by using compounds specifically targeting these, thus limiting their action on healthy cells. Targeted therapies are emerging and many clinical trials targeting these pathways, frequently involved in chemoresistance, have been tested on gynecological cancers. Despite some targets being less efficient than expected as mono-therapies, the combination of compounds seems to be the promising avenue. For instance, we demonstrate using ChIP-seq analysis that estrogen downregulate tumor suppressor Par-4 in hormone-dependent cells by directly binding to its DNA regulatory elements and inhibiting estrogen signaling could reinstate Par-4 apoptosis-inducing abilities. This review will focus on the chemoresistance mechanisms and the clinical trials of targeted therapies associated with these, specifically for endometrial and ovarian cancers.

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Section: Chemoresistance In Gynecological Cancersmentioning

confidence: 99%

Section: Targeted Therapies To Overcome Chemoresistancementioning

confidence: 99%

Chemoresistance and targeted therapies in ovarian and endometrial cancers

2016

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“…“Sandwich therapy” is NACT followed by interval debulking surgery and post-surgical chemotherapy. [ 13 , 38 ] Despite clinical and laboratory indicators to predict treatment response and prognosis, patients presented with varied therapeutic outcomes after “sandwich therapy.” [ 13 , 14 , 39 ]…”

Section: Discussionmentioning

confidence: 99%

Incidence of venous thromboembolism following the neoadjuvant chemotherapy regimen for epithelial type of ovarian cancer

et al. 2017

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This study aims to analyze the risk of venous thromboembolism (VTE) in patients receiving neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer (EOC).A retrospective audit was conducted examining 147 patients treated for EOC. Surgical treatment with curative intent, with or without NACT and adjuvant chemotherapy, is the treatment approach, which was modified according to the patient's condition. The incidence of VTE with the most commonly used chemotherapy regimen, carboplatin, cisplatin, paclitaxel, docetaxel, and others were evaluated.This study found a 13.6% incidence of VTE in patients undergoing therapy with curative intent for EOC. No association was seen between NACT and VTE compared to VTE after standard treatment: 2/16 (12.5%) vs 5/131 (3.8%) (P = .16). Univariate and multivariate analyses also demonstrated that NACT has no risk for VTE with odds ratio (OR) = 0.89 (95% CI = 0.18–4.28) and P = 1. Results did not vary significantly with the type of chemotherapy used. Furthermore, increased incidence of VTE as an incidental finding supports the well-established role of malignancy in VTE occurrence. Univariate and multivariate analyses demonstrated that VTE occurred more frequently in menopausal women than nonmenopausal women (17.9% vs 5.8%) with OR = 3.55 (95% CI = 0.99–12.78) and P = .04 in patients aged ≥60 (19.3% vs 10%) with OR = 2.15 (95% CI = 0.83–5.57) and P = .13 but is not statistically significant.We conclude that NACT has no association with VTE and the currently used common chemotherapeutic drug combinations for ovarian cancer carry the minimal risk of thromboembolic events.

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“…Also, the delivery of the combination of wt p53 cytotoxic and helper peptides on matured autologous DC is expected to improve antigen presentation to T cells in the context of strong adjuvant effects needed for improving the vaccine efficacy. However, since the wt p53 peptides are expressed at low levels in normal tissues, vaccines targeting p53 peptides may have to overcome a high level of immunologic tolerance to self (45). Therefore, the three vaccine administrations used in the present study might be insufficient for induction of a detectable and persistent response.…”

Section: Discussionmentioning

confidence: 99%

Phase I Dendritic Cell p53 Peptide Vaccine for Head and Neck Cancer

Schuler

Harasymczuk

Visús

et al. 2014

Clinical Cancer Research

130

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Background p53 accumulation in head and neck squamous cell carcinoma (HNSCC) cells creates a targetable tumor antigen. Adjuvant dendritic cell (DC)-based vaccination against p53 was tested in a phase I clinical trial. Methods Monocyte-derived DC from 16 patients were loaded with two modified HLA-class I p53 peptides (Arm 1); additional T-helper(Th) tetanus toxoid peptide (Arm 2) or additional Th wt p53-specific peptide (Arm 3). Vaccine DC (vDC) were delivered to inguinal lymph nodes at 3 time points. Vaccine (vDC) phenotype, circulating p53-specific T-cells and regulatory T-cells (Treg) were serially monitored by flow cytometry and cytokine production by Luminex. vDC properties were compared to those of DC1 generated with an alternative maturation regimen. Results No grade II-IV adverse events were observed. Two-year disease-free survival (DFS) of 88% was favorable. p53-specific T-cell frequencies were increased post vaccination in 11/16 patients (69%), with IFN-γ secretion detected in 4/16 patients. Treg frequencies were consistently decreased (p=0.006) relative to pre-vaccination values. The phenotype and function of DC1 were improved relative to vDC. Conclusion Adjuvant p53-specific vaccination of HNSCC patients was safe and associated with promising clinical outcome, decreased Treg levels, and modest vaccine-specific immunity. HNSCC patients’ DC required stronger maturation stimuli to reverse immune suppression and improve vaccine efficacy.

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Immunologic aspect of ovarian cancer and p53 as tumor antigen

Cited by 32 publications

References 133 publications

Chemoresistance and targeted therapies in ovarian and endometrial cancers

Chemoresistance and targeted therapies in ovarian and endometrial cancers

Incidence of venous thromboembolism following the neoadjuvant chemotherapy regimen for epithelial type of ovarian cancer

Phase I Dendritic Cell p53 Peptide Vaccine for Head and Neck Cancer

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