testing on buccal swab to improve access to healthcare and cancer prevention: a performance evaluation.

Objective: ) genetic testing allows patients with high-grade serous ovarian cancer to receive appropriate medical management with molecular target therapy and prevention strategies. Most of the sequencing methods use blood as the primary source of germline DNA. Buccal swab emerged as an alternative collection device due to its convenient and non-invasive characteristics.

Oncologic Drugs Approval in Europe for Solid Tumors: Overview of the Last 6 Years.

(1) Background: Drug development in oncology is changing rapidly. The aim of the present study was to provide an insight into the features of anti-tumor drugs approved in Europe; (2) Methods: We included all the indications for solid tumors issued by the European Medicines Agency (EMA) between 2015 and 2020. We extracted data from European Public Assessments Reports (EPAR), including drug name, mechanism of action, setting, features of pivotal clinical trials, primary end-points, quality of life (QoL); (3) Results: In the explored period, EMA issued 132 new indications (81 indications' extensions) for 62 oncology drugs.

Breast Cancer Drug Approvals Issued by EMA: A Review of Clinical Trials.

Breast cancer represents the first cause of cancer worldwide and the leading cause of cancer mortality for women. Therefore, new therapies are needed to improve the prognosis of women diagnosed with this disease. In this review, we summarize the new drug indications for the treatment of breast cancer approved by European Medicines Agency between January 2015 and June 2021.

Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment.

Adjuvant therapy recommendations for endometrial cancer were historically based on the individual patient's risk of disease recurrence using clinicopathologic factors such as age, stage, histologic subtype, tumor grade, and lymphovascular space invasion. Despite the excellent prognosis for early stages, considerable under- and overtreatment remains. Integrated genomic characterization by the Cancer Genome Atlas (TCGA) in 2013 defined four distinct endometrial cancer subgroups (POLE mutated, microsatellite instability, low copy number, and high copy number) with possible prognostic value.

Oligometastatic Breast Cancer: How to Manage It?

Breast cancer (BC) is the most frequent cancer among women and represents the second leading cause of cancer-specific death. A subset of patients with metastatic breast cancer (MBC) presents limited disease, termed 'oligometastatic' breast cancer (OMBC). The oligometastatic disease can be managed with different treatment strategies to achieve long-term remission and eventually cure.

Neoadjuvant chemoteraphy in unresectable ovarian cancer with olaparib and weekly carboplatin plus paclitaxel: a phase II, open label multicenter study (NUVOLA trial).

Background: Neoadjuvant chemotherapy with interval debulking surgery represents an alternative treatment for advanced ovarian cancer. Currently, there are few data about the use of poly adenosine diphosphate-ribose polymerase inhibitors in the neoadjuvant setting.

Primary Objective: To evaluate whether the administration of olaparib in combination with standard chemotherapy in the neoadjuvant setting can improve tumor response.

Role of Immune Checkpoint Inhibitors in Cervical Cancer: From Preclinical to Clinical Data.

Human papillomavirus (HPV) infection is the recognized cause of almost all cervical cancers. Despite the reduction in incidence due to a wide use of screening programs and a specific vaccine, the prognosis of cervical cancer remains poor, especially for late-stage and relapsed disease. Considering the elevated rates of PD-L1 expression in up to 80% of cervical cancers, a strong rationale supports the use of immunotherapy to restore the immune response against tumor.

The Role of Artificial Intelligence in Managing Multimorbidity and Cancer.

Traditional healthcare paradigms rely on the disease-centered approach aiming at reducing human nature by discovering specific drivers and biomarkers that cause the advent and progression of diseases. This reductive approach is not always suitable to understand and manage complex conditions, such as multimorbidity and cancer. Multimorbidity requires considering heterogeneous data to tailor preventing and targeting interventions.

Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors.

Ovarian cancer treatment strategy is mainly based on three pillars: cytoreductive surgery, platinum-based chemotherapy, and targeted therapies. The latter in the last decade has provided a remarkable improvement in progression free patients and, hopefully, in overall survival. In particular, poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors exploit BRCA 1/2 mutations and DNA damage response deficiencies, which are believed to concern up to 50% of high grade epithelial ovarian cancer cases.

The BRCA1 c.788G > T (NM_007294.4) variant in a high grade serous ovarian cancer (HGSOC) patient: foods for thought.

In this report we described the case of a BRCA1/2 (BRCA) molecular testing performed on tumor sample in a High Grade Serous Ovarian Cancer (HGSOC) patient with two different Next Generation Tumor Sequencing (NGTS) pipelines. The two clinical reports leaded to apparently different BRCA status, providing important foods for thought. After NGTS, the gene sequencing information (i.

Oregovomab: an investigational agent for the treatment of advanced ovarian cancer.

: Ovarian cancer (OC) represents the leading cause of death among gynecological cancers. Despite novel compound classes like vascular endothelial growth factor (VEGF) inhibitors or poly-ADP ribose polymerase (PARP) inhibitors are available, which improve significantly efficacy of platinum-based chemotherapy, OC prognosis remains poor and innovative strategies are needed. The induction of tumor specific immune response with a therapeutic intent is a very challenging approach.

Immunotherapy in gynecological cancers.

Immunotherapy has changed the natural history of several malignancies that, a decade ago, had a very poor prognosis, such as lung cancer and melanoma. Consequently, many attempts have been done to expand the indications of immunotherapy agents, predominantly immune checkpoint inhibitors (ICIs), in other cancers, including gynecological malignancies. Alongside promising results in cervical and endometrial neoplasms, there are not clear data on the benefit of ICIs as single agent or in combination with antiangiogenic agents in ovarian cancer (OC) and ongoing trials are focusing on combining ICIs with standard chemotherapy or PARP inhibitors.

Newly diagnosed ovarian cancer: Which first-line treatment?

Poly ADP -Ribose Polymerase (PARP) inhibitors (PARPi) were firstly licensed for maintenance treatment in recurrent, platinum-sensitive, platinum responsive epithelial ovarian cancer patients, harboring or not a BRCA mutation. Three new phase III trials - PAOLA1/ENGOT-OV25, PRIMA/ENGOT-OV26 and VELIA/GOG-3005 - showed that there is a role for PARPi also in first-line setting, as maintenance or in combination with platinum-based chemotherapy. Nevertheless the published trials raised several questions on what is the best treatment according to the molecular and clinical characteristics of the treated patients.

Emerging role of immune checkpoint inhibitors in the treatment of ovarian cancer.

Introduction: In recent years, ovarian cancer (OC) treatment has been enriched with many new target therapies, most of all antiangiogenic drugs and PARP inhibitors (PARPis), which have literally changed the natural history of the disease. The impressive results of immunotherapy in other malignancies, mainly melanoma and lung cancer, and the good signals of activity in gynecological neoplasms like cervical and microsatellite instable (MSI-H) endometrial cancer, opened the space to the introduction of immune-stimulatory drugs in ovarian cancer.

Area Covered: The goal of this article is to summarize the newest evidence on the use of immune check point inhibitors in OC trying to explain why, at present, this strategy has failed to improve clinical outcome and focusing on the possible strategies to overcome treatment failure.

Ovarian cancer predisposition beyond BRCA1 and BRCA2 genes.

Several genes associated with hereditary ovarian cancer have been discovered as a result of the work done with next generation sequencing. It is estimated that approximately 23% of ovarian carcinomas have a hereditary predisposition. The most common hereditary condition is represented by germline mutations in BRCA1 or BRCA2 genes that account for 20-25% of high grade serous ovarian cancer.

Feasibility of tumor testing for BRCA status in high-grade serous ovarian cancer using fresh-frozen tissue based approach.

Objective: For many years, BRCA mutational status has only been considered as a predictor of ovarian cancer susceptibility and as a prognostic factor. Nonetheless, in the era of precision medicine, it has also become a predictive biomarker of response to platinum-based-chemotherapy and, more recently, to PARP-inhibitors, also in the frontline setting. We assessed the feasibility of a fresh frozen tissue-based-BRCA-screening workflow in a tertiary referral center.

Integration of PARP-inhibitors in ovarian cancer therapy.

Poly-ADP-ribose polymerase inhibitors (PARP-I) represent one of the most attractive and promising class of biological agents studied both in relapsed ovarian cancer (OC) and in the advanced setting. The availability of this new class of drugs has changed the clinical management of OC ensuring an unprecedented advance in such an aggressive cancer. Three oral PARP-I are currently available: olaparib, niraparib and rucaparib.

PTEN and Gynecological Cancers.

PTEN is a tumour suppressor gene, and its loss of function is frequently observed in both heritable and sporadic cancers. It is involved in a great variety of biological processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism. A better understanding of PTEN activity and regulation has therefore emerged as a subject of primary interest in cancer research.

New medical approaches in advanced ovarian cancer.

Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecologic malignancy. Most women with advanced epithelial ovarian cancer will experience many episodes of recurrent disease with progressively shorter disease-free intervals. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more.

Emerging drugs for ovarian cancer.

Importance Of The Field: Ovarian cancer has the highest mortality of all female reproductive tract cancers, which reflects both the absence of proven ovarian cancer screening tests and the development of drug-resistant cancer cell. Apart from varying the dosages, schedules, mode of delivery and combinations of existing drugs, efforts must continue to identify signaling pathways in tumor cells sufficiently different from normal cells that can be a target for maximizing tumor kill and minimizing toxicity.

Areas Covered In This Review: Some of the most important cellular pathways are analyzed and discussed and the most interesting clinical trials, both closed and ongoing, described.

Brostallicin (PNU-166196), a new minor groove DNA binder: preclinical and clinical activity.

Brostallicin (PNU-166196), a-bromo-acrylamido tetra-pyrrole derivative, showed high cytotoxic potency and myelotoxicity dramatically reduced compared with other minor groove DNA-binding agents. In the presence of high intracellular glutathione concentrations, which are associated with resistance to chemotherapy, brostallicin performs a DNA minor groove attack leading to alkylation of DNA nucleophilic functions. In preclinical models, the antitumor activity of brostallicin has been tested in ovarian cancer xenografts, L1210 murine leukemia models, renal, colon and prostatic cancer cells and glutathione-S-transferase (GST) transfected human breast carcinoma cells.

Review role of topotecan in gynaecological cancers: current indications and perspectives.

Background: Ovarian cancer is the fourth cause of death from gynaecological cancer and cervical cancer is the first in women <45 years old in developing countries. The aim of this article is to review the role of topotecan (Hycamtin), a semi-synthetic alkaloid derivative of camptothecin, in ovarian and cervical cancer in monotherapy and in combination.

Methods: This article reviews the mechanism of action, pharmacokinetics, toxicity and efficacy of topotecan.