SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Expert review of anticancer therapy

0

T-cell checkpoint inhibition as a cancer treatment approach has been the main breakthrough in cancer treatment during the last years. Since the approval of the first commercial CTLA-4 antibody ipilimumab in 2011 for the treatment of melanoma, research and drug development in this field has accelerated massively. In 2014 the US Food and Drug Administration (FDA) approved the first PD-1 targeting agent, namely pembrolizumab, shortly followed by nivolumab. Areas covered: Nivolumab is a fully human immunoglobulin G4 anti-PD-1 monoclonal antibody which is approved for multiple advanced malignancies, including melanoma, non-small cell lung cancer, renal cell cancer, Hodgkin’s lymphoma, squamous head and neck cancer and urothelial carcinoma. In September 2017 nivolumab was approved by the FDA for liver cancer as a second line treatment after failure of sorafenib based on the data of the multi-cohort phase ½ trial CheckMate-040. This article reviews the concept of immunotherapy in liver cancer with focus on nivolumab. Expert commentary: Immunotherapy in hepatocellular carcinoma provides a new treatment option for patients in advanced stages besides sorafenib and other newly approved tyrosine kinase inhibitors. More data concerning effectivity and choosing the right patients for immunotherapy is warranted in the future.

0

Although the majority of women with endometrial cancer have a favourable prognosis due to early symptoms, 15-20% have high-risk disease features and are at increased risk of recurrence. In order to improve prognosis for these patients, several trials have compared chemotherapy (CT), radiotherapy (RT) or the combination of CTRT. Areas covered: This review focuses on the current evidence on adjuvant treatment for women with high-risk endometrial cancer and future perspectives. Expert commentary: For stage I-II high-risk endometrial cancer, external beam radiotherapy ensured good local control and no significant benefit in progression-free or overall survival was found with the addition of chemotherapy in 2 recent randomised trials. For women with stage III disease, the combination of chemotherapy and radiotherapy improved progression-free survival with a non-significant improvement of overall survival. Adjuvant chemotherapy alone resulted in higher rates of pelvic and para-aortic recurrence. More toxicity and reduced quality of life was found during and after adjuvant CTRT. It is essential to discuss the benefits and disadvantages of chemotherapy and radiotherapy with individual patients for shared decision making. Translational research is ongoing to further characterize individual tumours, identify sensitivity to (immuno)therapies and find new treatment targets to improve outcomes.

0

Pancreatic cancer is a highly malignant disease with high treatment resistance. Many patients are diagnosed in a very advanced state, and few patients can be curatively resected. With FOLFIRINOX and nab-paclitaxel plus gemcitabine, the prognosis of advanced pancreatic cancer has improved, yet many patients cannot survive longer than a year. Therefore, new therapeutic approaches are needed. Cancer vaccine therapy is characterized by controlling cancer by a cancer-specific immune reaction with few adverse events. Thus, a cancer peptide vaccine is considered promising for pancreatic cancer patients, who are often in poor general condition at diagnosis. Areas covered: This article reviews available data from recent clinical trials of the novel cancer vaccine therapy in combination with traditional chemotherapy or radiotherapy for pancreatic cancer, and the prospect will be described. Expert Commentary: In clinical trials of the novel cancer vaccine therapy in combination with traditional therapy, many studies have failed to outperform traditional therapy, although some effects were recognized in subgroups. what is necessary in the future for cancer vaccine therapy to improve the prognosis of pancreatic cancer is combination of immune-checkpoint blockade to release immune escape mechanism and combination with strong multi-drug combination chemotherapy.

0

Gastric cancer is one of a few gastrointestinal malignancies in which immunotherapy has shown meaningful activity. Pembrolizumab is the first and only immune checkpoint inhibitor to be FDA-approved in gastric cancer. Areas Covered: This review summarizes the current and emerging clinical evidence for immune checkpoint inhibitors in advanced and metastatic gastric cancer, with a focus on pembrolizumab. Expert Commentary: Pembrolizumab has shown impressive activity in the third-line treatment of locally advanced and metastatic gastric cancer. It is currently being studied as upfront therapy in combination with chemotherapy. The emerging understanding of the molecular alterations and tumor immune microenvironment as predictors of immunotherapy response in gastric cancer are discussed. The impact of gastric mucosal dysbiosis on gastric carcinogenesis and the modulation of immunotherapy response by the gut microbiome are also reviewed.

0

Ovarian cancer patients with relapse 6-12 months after last platinum treatment, who have received bevacizumab consolidation and are not BRCA mutant, represent a considerable therapeutic challenge.

0

In patients with recurrent ovarian cancer, there are certain situations where further surgery and/or next-line platinum-based chemotherapy is not feasible or is not the best option. Multidisciplinary teams have a key role in reviewing available options and selecting the most appropriate intervention.

0

The challenges of managing relapsed ovarian cancer increase as more advanced lines of chemotherapy are achieved.

0

Patient-reported outcomes (PROs), including quality-of-life considerations, are increasingly becoming key factors in clinical decision making. Areas covered: This review provides an overview of the current status of PROs in guiding clinical trial design and clinical decision making in patients with ovarian cancer and previews the future potential of PROs in these settings. Expert commentary: In ovarian cancer, considerable discord exists between patients and physicians regarding perceived symptom burden. During maintenance therapy, it is important that the most appropriate PROs (i.e. endpoints and respective measuring tools) are selected to evaluate patients. Research continues into identifying PROs most likely to facilitate and enhance reporting of symptoms, adverse events, and subjective benefit. Some recent studies performed in ovarian cancer, such as the SOLO2/ENGOT-Ov21 and AURELIA trials, have reported valuable PRO data pertaining to the Trial Outcome Index (TOI) score, quality-adjusted progression-free survival (QAPFS), and time without symptoms and toxicity (TWiST). In future, PROs are likely to become increasingly important in clinical trial design, regulatory procedures, and provision of valuable prognostic information to patients and physicians in clinical practice.

0

Protein kinases are involved in various cellular functions including metabolism, cell cycle regulation, survival, and differentiation. Dysregulation of protein kinases is implicated in various processes of carcinogenesis. The advent of protein kinase inhibitors in cancer therapy has led to a paradigm shift in how we treat cancer. There are several protein kinase inhibitors that have been approved by FDA in the last few decades. Areas Covered: This article provides a review of the clinical benefits and side effect profiles of FDA approved protein kinase inhibitors as of December 2017 for the well-known oncogenic protein kinases. The role of the respective oncogenic protein kinases in carcinogenesis and cancer progression were searched in PubMed and discussed. The relevant and landmark clinical trials mostly phase III trials of protein kinase inhibitors leading up to the FDA approval were PubMed searched and discussed. Expert Commentary: Further understanding of the molecular origin of cancers would help us identify new targets, while clinical trials trying to identify the appropriate sequence of available kinase inhibitor would make better use of current protein kinase inhibitor armamentarium. Also, testing these drugs in the adjuvant setting in patients with high risk of recurrence might offer some clinical benefit. Development of resistance, side effects and cost are major limitations of protein kinase inhibitors, therefore understanding of the molecular mechanisms of resistance and designing protein kinase inhibitors to obviate the resistance would help overcome the resistance. Finally, collaboration between international organizations for cancer research and voluntary and charity organizations might help reduce the cost.

0

A defining hallmark of cancer is aberrant cell proliferation. Efforts to understand the generative properties of cancer cells span all biological scales: from genetic deviations and alterations of metabolic pathways, to physical stresses due to overcrowding, as well as the effects of therapeutics and the immune system. While these factors have long been studied in the laboratory, mathematical and computational techniques are being increasingly applied to help understand and forecast tumor growth and treatment response. Advantages of mathematical modeling of proliferation include the ability to simulate and predict the spatiotemporal development of tumors across multiple experimental scales. Central to proliferation modeling is the incorporation of available biological data and validation with experimental data. Areas covered: We present an overview of past and current mathematical strategies directed at understanding tumor cell proliferation. We identify areas for mathematical development as motivated by available experimental and clinical evidence, with a particular emphasis on emerging, non-invasive imaging technologies. Expert commentary: The data required to legitimize mathematical models are often difficult or (currently) impossible to obtain. We suggest areas for further investigation to establish mathematical models that more effectively utilize available data to make informed predictions on tumor cell proliferation.