paywalled: Antigen-specific immunotherapy in ovarian cancer and p53 as tumor antigen.

Antigen-specific immunotherapy in ovarian cancer and p53 as tumor antigen.:

Abstract
Immunotherapy for ovarian cancer is one of the new treatment strategies currently investigated in epithelial ovarian cancer. This review discusses the results of different immunization strategies, identifies possible drawbacks in study design and provides potential solutions for augmentation of clinical efficacy. A potential target for cancer immunotherapy is p53, as approximately 50% of ovarian cancer cells carry p53 mutations. Therefore we review the immunological and clinical responses observed in ovarian cancer patients vaccinated with p53 targeting vaccines in particular. In most studies antigen-specific vaccine-induced immunological responses were observed. Unfortunately, no clinical responses with significant reduction of tumor-burden have been reported. Based on the currently available results we emphasize the necessity of multimodality treatment of ovarian cancer, combining classical cytoreductive surgery, (neo) adjuvant chemotherapy, immunotherapy and/or targeted therapy.

still recruiting: A (phase 11) Study of MK-1775 in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone for Participants With Platinum-Sensitive Ovarian Tumors With the P53 Gene Mutation (MK-1775-004) - Full Text View - ClinicalTrials.gov

Official Title:
A Randomized, Phase II Study Evaluating MK-1775 in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Adult Patients With Platinum Sensitive p53 Mutant Ovarian Cancer

 Criteria

Inclusion Criteria:

• Histologically confirmed non-low grade, non-borderline (low malignant potential) ovarian cancer which has progressed after paclitaxel / carboplatin therapy.
• Platinum-sensitive disease. The earliest evidence of progression must have occurred at least 6 months following the completion of the most recent platinum-based treatment.
• Measurable disease.
• Available tumor sample(s).
• Performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Adequate organ function.

p53 Signature and Serous Tubal In-situ Carcinoma in Cases of Primary Tubal and Peritoneal Carcinomas and Serous Borderline Tumors of the Ovary

UK media: Sufferers of ovarian cancer get new hope - p53 gene

Long-term clinical and immunological effects of p53-SLP® vaccine in ovarian cancer patients

Abstract

Vaccine-induced p53-specific immune responses were previously reported to be associated with improved response to secondary chemotherapy in small cell lung cancer patients. We investigated longterm clinical and immunological effects of the p53-SLP® vaccine in recurrent ovarian cancer patients. Twenty patients were immunized with the p53-SLP® vaccine between July 2006 and August 2007.
Follow-up information on patients was obtained. Clinical responses to secondary chemotherapy after p53-SLP® immunizations was determined by computerized tomography and/or tumour marker levels (CA125). Disease-specific survival was compared with a matched historical control group. Immune responses were analysed by flow cytometry, proliferation assay, IFN-γ ELISPOT and/or cytokine bead array. Lymphocytes cultered from skin biopsy were analysed by flow cytometry and proliferation assay.
Of twenty patients treated with the p53-SLP® vaccine, seventeen were subsequently treated with chemotherapy. Eight of these volunteered another blood sample. No differences in clinical response rates to secondary chemotherapy or disease-specific survival were observed between immunized patients and historical controls (p=0.925, resp. p=0.601). P53-specific proliferative responses were observed in 5/8 patients and IFN-γ production in 2/7 patients. Lymphocytes cultured from a prior injection site showing inflammation during chemotherapy did not recognise p53-SLP®. Thus treatment with the p53- SLP® vaccine does not affect responses to secondary chemotherapy or survival, although p53-specific T-cells do survive chemotherapy.

Risk factors for non-invasive lesions of the fallopian tube in BRCA mutation carriers (study of 173 BRCA mutation carriers)

Objective

To identify risk factors for the presence of a non-invasive lesion of the fallopian tube in women with a BRCA1 or BRCA2 mutation.

Conclusion

The prevalence of tubal p53 signature and TIC (a tubal intra-epithelial carcinoma (TIC))  increases with age at salpingectomy and with BMI. Oral contraceptive use is associated with a decrease in the prevalence of TICs.

Objective To identify risk factors for the presence of a non-invasive lesion of the fallopian tube in women with a BRCA1 or BRCA2 mutation (abstract)

Objective

To identify risk factors for the presence of a non-invasive lesion of the fallopian tube in women with a BRCA1 or BRCA2 mutation.

Conclusion

The prevalence of tubal p53 signature and TIC (tubal intra-epithelial carcinoma)  increases with age at salpingectomy and with BMI. Oral contraceptive use is associated with a decrease in the prevalence of TICs.

p53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer

IMPACT: Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival.

A Mechanism Behind Negative Tumor Suppressor Gene Function Identified - p53

Note: the p53 gene has been studied extensively for decades including p53 vaccines, hopefully new research will move research on p53 quickly as its implications in cancer will have a great impact

Abstract / full free text: Expression signatures of TP53 mutations in serous ovarian cancers

Conclusions This represents the first attempt to define a genomic signature of TP53 mutation in ovarian cancer. Patterns of gene expression characteristic of TP53 mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of TP53 mutation in breast cancer.

Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.

Note: in research/technical

Molecular Profiling Uncovers a p53-Associated Role for MicroRNA-31 in Inhibiting the Proliferation of Serous Ovarian Carcinomas and Other Cancers

Note: miR-31 (rna/genome/gene)

"Our findings reveal that loss of miR-31 is associated with defects in the p53 pathway and functions in serous ovarian cancer and other cancers, suggesting that patients with cancers deficient in p53 activity might benefit from therapeutic delivery of miR-31."

p53 Autoantibodies as Potential Detection and Prognostic Biomarkers in Serous Ovarian Cancer

CONCLUSIONS: Antibodies to p53 are detected in the sera of 42% of patients with advanced serous ovarian cancer.
Impact: Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival.
Cancer Epidemiol Biomarkers Prev

full free access: TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use — Cold Spring Harbor Perspectives in Biology

Somatic TP53 mutations occur in almost every type of cancer at rates from 38%–50% in ovarian and..........TP53 mutations, but not p53 positive immunohistochemistry (IHC), have been consistently associated with poor prognosis in cancers such as breast, colorectal, head and neck, and leukemia.....In terms of clinical applications, TP53 mutations have proven to be extremely complex biomarkers. Despite impressive progress in mechanistic understanding of p53 structure and function, p53 research has not yet generated applications of wide impact on cancer management and therapy."