scholarly journals Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer

2021 ◽  
Vol 11 (2) ◽  
pp. 149 ◽  
Author(s):  
Christen A. Khella ◽  
Gaurav A. Mehta ◽  
Rushabh N. Mehta ◽  
Michael L. Gatza
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Therapeutic Response ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Signaling Networks ◽  
Molecular Heterogeneity ◽  
Breast And Ovarian Cancer ◽  
Recent Advances ◽  
The Impact

The underlying molecular heterogeneity of cancer is responsible for the dynamic clinical landscape of this disease. The combination of genomic and proteomic alterations, including both inherited and acquired mutations, promotes tumor diversity and accounts for variable disease progression, therapeutic response, and clinical outcome. Recent advances in high-throughput proteogenomic profiling of tumor samples have resulted in the identification of novel oncogenic drivers, tumor suppressors, and signaling networks; biomarkers for the prediction of drug sensitivity and disease progression; and have contributed to the development of novel and more effective treatment strategies. In this review, we will focus on the impact of historical and recent advances in single platform and integrative proteogenomic studies in breast and ovarian cancer, which constitute two of the most lethal forms of cancer for women, and discuss the molecular similarities of these diseases, the impact of these findings on our understanding of tumor biology as well as the clinical applicability of these discoveries.

The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

2018 ◽  
Vol 18 (6) ◽  
pp. 832-836
Author(s):  
Giuseppe Buono ◽  
Francesco Schettini ◽  
Francesco Perri ◽  
Grazia Arpino ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Translational Research ◽  
Cell Biology ◽  
Cancer Biology ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

Drug resistance in clinical practice: patterns of treatment failure in advanced breast and ovarian cancer.

1986 ◽  
Vol 4 (6) ◽  
pp. 952-957 ◽  
Author(s):  
P R Harnett ◽  
F Kirsten ◽  
M H Tattersall
Keyword(s):  
Ovarian Cancer ◽  
Treatment Failure ◽  
Disease Progression ◽  
Progressive Disease ◽  
Complete Response ◽  
Advanced Breast ◽  
New Disease ◽  
Breast Cancer Patients ◽  
Breast And Ovarian Cancer ◽  
Disease Site

We have analyzed the patterns of disease progression in patients with advanced breast and ovarian cancer receiving systemic therapy. Approximately 50% of patients developed progressive disease in a new, rather than a previously documented, disease site. Even when disease progressed in a previously involved disease site, in only half the cases was this identified as the bulk disease site before commencing treatment. The CNS was rarely a new site of disease progression in our patients, a finding that contrasts with a report that identified the CNS as the predominant new disease site in advanced breast cancer patients relapsing following a complete response. Progression of disease on second line treatment commonly occurred at sites of known disease. A number of factors influencing the pattern of disease progression have been examined. Disease progression on endocrine therapy tended to be more common in a previously involved disease site than in patients receiving cytotoxic therapy. There was a trend for patients who progressed within 6 months of chemotherapy to do so in an old site, whereas new disease sites predominated among those progressing later. Strategies for overcoming the causes of treatment failure should take account of the patterns of disease progression. Our results question the wisdom of always ceasing existing therapy when progressive disease is first documented.

Trials With Impact on Clinical Management: First Line

2009 ◽  
Vol 19 (Suppl 2) ◽  
pp. S55-S62 ◽  
Author(s):  
Michael A. Bookman
Keyword(s):  
Ovarian Cancer ◽  
Cancer Biology ◽  
Treatment Options ◽  
Tumor Biology ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Weekly Dose ◽  
Primary Therapy ◽  
Phase 3 ◽  
Standard Regimen

Introduction:Advanced-stage epithelial ovarian cancer is generally managed with cytoreductive surgery and chemotherapy consisting of carboplatin and paclitaxel. Although initially responsive, most tumors recur and demonstrate progressive chemotherapy resistance. During the last 20 years, many thousands of women have participated in international front-line phase 3 trials that have contributed to our understanding of ovarian cancer biology and helped to define optimal treatment strategies. Emerging data from these trials need to be interpreted within an evolving paradigm of cancer biology, disease management, and availability of clinical resources.Methods:Survey of recent phase 3 trials and emerging principles of ovarian tumor biology.Results:There is no evidence that adding a third cytotoxic agent improves clinical outcomes. However, weekly dose-dense scheduling of paclitaxel appears superior to standard dosing.Conclusion:Primary therapy with carboplatin and paclitaxel remains a well-tolerated standard regimen, including the option of weekly paclitaxel dosing. Data are awaited from completed trials incorporating bevacizumab. Emerging biological paradigms will contribute to individualized treatment options in the future.

scholarly journals SEOM clinical guidelines in hereditary breast and ovarian cancer (2019)

2019 ◽  
Vol 22 (2) ◽  
pp. 193-200 ◽  
Author(s):  
S. González-Santiago ◽  
◽  
T. Ramón y Cajal ◽  
E. Aguirre ◽  
J. E. Alés-Martínez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Genetic Diagnosis ◽  
Treatment Strategies ◽  
Parp Inhibitors ◽  
Breast And Ovarian Cancer ◽  
Brca Mutations ◽  
Clinical Criteria ◽  
Therapeutic Implications ◽  
New Genes

AbstractMutations in BRCA1 and BRCA2 high penetrance genes account for most hereditary breast and ovarian cancer, although other new high-moderate penetrance genes included in multigene panels have increased the genetic diagnosis of hereditary breast and ovarian cancer families by 50%. Multigene cancer panels provide new challenges related to increased frequency of variants of uncertain significance, new gene-specific cancer risk assessments, and clinical recommendations for carriers of mutations of new genes. Although clinical criteria for genetic testing continue to be largely based on personal and family history with around a 10% detection rate, broader criteria are being applied with a lower threshold for detecting mutations when there are therapeutic implications for patients with breast or ovarian cancer. In this regard, new models of genetic counselling and testing are being implemented following the registration of PARP inhibitors for individuals who display BRCA mutations. Massive sequencing techniques in tumor tissue is also driving a paradigm shift in genetic testing and potential identification of germline mutations. In this paper, we review the current clinical criteria for genetic testing, as well as surveillance recommendations in healthy carriers, risk reduction surgical options, and new treatment strategies in breast cancer gene-mutated carriers.

The impact of the medicare benefits schedule on genetic testing in hereditary breast and ovarian cancer: An audit of test request practices in Western Australia

Pathology ◽  
2018 ◽  
Vol 50 ◽  
pp. S100
Author(s):  
Sarah L. Nickerson ◽  
Jamie-Lee Ricciardi ◽  
Ratna Dubey ◽  
Deborah Norman ◽  
Natasha Buzzacott ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Western Australia ◽  
Breast And Ovarian Cancer ◽  
The Impact ◽  
Test Request

Changes in the fucose content of haptoglobin in breast and ovarian cancer: Association with disease progression

1994 ◽  
Vol 1 (1) ◽  
pp. 37-43 ◽  
Author(s):  
E. Dargan ◽  
S. Thompson ◽  
B. M. J. Cantwell ◽  
R. G. Wilson ◽  
G. A. Turner
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Breast And Ovarian Cancer ◽  
Fucose Content

scholarly journals The castration level of testosterone and hormonal resistance of prostate cancer in androgen deprivation therapy

2020 ◽  
pp. 100-108
Author(s):  
I. G. Rusakov ◽  
A. A. Gritskevich ◽  
T. P. Baitman ◽  
S. V. Mishugin
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Treatment Strategies ◽  
Significant Risk ◽  
Androgen Deprivation ◽  
Early Detection Of Disease ◽  
Biomarker Analysis ◽  
The Impact

This review is dedicated to the impact of modern achievements on the definition and diagnostics of castration-resistant prostate cancer (PCa) (CRPC), prognostic factors for its progression, and treatment strategies.It was proven with new sensitive methods of diagnostics that surgical castration (CS) decreases serum testosterone (T) levels to < 20 ng/dL, while achieving T < 20 ng/dL improves outcomes and delays the development of CRPC. Regular assessment of the T level makes it possible to understand whether this androgen is adequately suppressed in the setting of potential progression of CRPC, given that late dosing may lead to an increase in T level. Improved imaging techniques and biomarker analysis enable early detection of disease progression. Prognostically significant risk factors for CRPC progression include Gleason score, the extent of metastatic spread, hereditary characteristics such as gene mutations affecting androgen receptor (AR) amplification or DNA repair deficiency mutations, prostate-specific antigen (PSA) kinetics, and biomarker levels. Today, treatment options for CRPC have gone beyond androgen deprivation therapy (ADT) to include therapy that blocks T-synthesis and/or suppresses its activity through various mechanisms. Future directions include therapies using new biological targets, drug combinations and personalized therapies. It is necessary to assess the possible reasons for the difference in the pharmacodynamics and pharmacokinetics of androgendeprivation drugs, to study the features of the processes of destruction of drugs under the action of endogenous enzymes and resorption in the subcutaneous or muscle depot, which may cause the resistance to therapy.The aim of improved treatment and diagnostic options for PCa is to delay its progression to CRPC and to prolong patient survival. Rethinking of the castration concept and advances in understanding the biology of disease progression make it necessary to revise diagnostic and treatment strategies. ADT is a fundamental vector of treatment, and it should be continued even if some new ways of treatment for CRPC are introduced.

scholarly journals Interleukin-34 expression in ovarian cancer: a possible correlation with disease progression

2019 ◽  
Vol 32 (3) ◽  
pp. 175-186 ◽  
Author(s):  
Hiraku Endo ◽  
Naoki Hama ◽  
Muhammad Baghdadi ◽  
Kozo Ishikawa ◽  
Ryo Otsuka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cell Lines ◽  
Cancer Tissues ◽  
The Impact

Abstract Ovarian cancer is the second-most lethal gynecological malignancy and the seventh-commonest cause of cancer-related death in women around the world. Most of the ovarian cancer patients are diagnosed at advanced stages and suffer from recurrence after primary cytoreductive surgery and standard first-line chemotherapy. Thus, the successful management of ovarian cancer patients requires the identification of factors that contribute to progression and relapse. Interleukin-34 (IL-34) is a novel cytokine that acts as a tissue-specific ligand of colony-stimulating factor-1 receptor (CSF-1R). In cancer, IL-34 exerts pro-tumorigenic functions that promote tumor growth, metastasis, angiogenesis, immune suppression and therapeutic resistance. In this study, we evaluate the impact of IL-34 on progression and survival of ovarian cancer patients. First, IL-34 was found to be expressed in several human ovarian cancer cell lines and cancer tissues from patients. The expression of IL-34 was enhanced by cytotoxic chemotherapy in ovarian cancer cell lines and cancer tissues from chemotherapy-treated ovarian cancer patients. Importantly, high IL-34 expression correlated with worse progression-free survival (PFS) and overall survival in different cohorts. The assessment of PFS based on a combination between IL34 expression and other related genes such as CSF1R and CD163 helped further to reach more statistical significance compared with IL34 alone. Furthermore, in the murine ovarian cancer cell HM-1 in vivo model, it was suggested that IL-34-derived tumor cells was correlated with tumor progression and survival by modulating the immune environment. Collectively, these findings indicate a possible correlation between IL-34 expression and disease progression in ovarian cancer patients and the mouse model.

Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues…

2016 ◽  
pp. 153-162 ◽  
Author(s):  
Renee Cowan ◽  
Dennis Chi ◽  
Sean Kehoe ◽  
Matthew Nankivell ◽  
Alexandra Leary
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Tumor Biology ◽  
Advanced Ovarian Cancer ◽  
Debulking Surgery ◽  
Primary Debulking Surgery ◽  
Platinum Based Chemotherapy ◽  
Patient Reported ◽  
The Impact

Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies.

scholarly journals Non-Coding Variants in BRCA1 and BRCA2 Genes: Potential Impact on Breast and Ovarian Cancer Predisposition

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 453 ◽  
Author(s):  
Elizabeth Santana dos Santos ◽  
François Lallemand ◽  
Leslie Burke ◽  
Dominique Stoppa-Lyonnet ◽  
Melissa Brown ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Predisposition ◽  
Gene Promoters ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Coding Regions ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Donor And Acceptor ◽  
The Impact

BRCA1 and BRCA2 are major breast cancer susceptibility genes whose pathogenic variants are associated with a significant increase in the risk of breast and ovarian cancers. Current genetic screening is generally limited to BRCA1/2 exons and intron/exon boundaries. Most identified pathogenic variants cause the partial or complete loss of function of the protein. However, it is becoming increasingly clear that variants in these regions only account for a small proportion of cancer risk. The role of variants in non-coding regions beyond splice donor and acceptor sites, including those that have no qualitative effect on the protein, has not been thoroughly investigated. The key transcriptional regulatory elements of BRCA1 and BRCA2 are housed in gene promoters, untranslated regions, introns, and long-range elements. Within these sequences, germline and somatic variants have been described, but the clinical significance of the majority is currently unknown and it remains a significant clinical challenge. This review summarizes the available data on the impact of variants on non-coding regions of BRCA1/2 genes and their role on breast and ovarian cancer predisposition.

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