Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma

Malignant Mesothelioma (MM) is a rare and aggressive form of tumour that affects the lining of the internal organs for which current treatments have not been proven to be very effective. P16(INK4A) tumour suppressor encoding CDKN2A gene is often downregulated in MM. This protein is a cyclin dependent kinase 4 and 6 inhibitor, that normally phosphorylates RB1, which has to be un-phosphorylated in order to block cell-cycle at G1 in normal cells. Adding CDK inhibitor molecules to MM in pre-clinical studies has been proven to restore the normal function of p16(INK4A), blocking thereby MM cell cycle at G1. Future randomised phase III studies with CDK4/6 inhibitors in MM carrying relevant CDK4/6, cyclin D1/3 or p16 aberrations will be warranted

Corticosteroid switch after progression on abiraterone acetate plus prednisone

Introduction: Abiraterone acetate plus prednisone is approved in metastatic castration-resistant prostate cancer. There is some evidence in favour of the steroid switch from prednisone to dexamethasone in patients who progressed whilst on abiraterone acetate plus prednisone or prednisolone. Materials and Methods: The aim of this review is to discuss the results from the clinical studies available, examining potential mechanisms of action and patient selection criteria for this treatment option. Results: A total of four studies were evaluated. Among possible eligibility criteria for steroid switch, we found: PSA progression without any radiological or clinical progression during abiraterone acetate + prednisone; no high-grade adverse events related to CYP-17 inhibition; and unfitness for chemotherapy or radium-223. Conclusion: Although large randomized prospective trials are warranted, steroid switch seems to offer a good option for certain patients treated with abiraterone acetate plus prednisone or prednisolone

Bevacizumab in small cell lung cancer

Comment on Italian, Multicenter, Phase III, Randomized Study of Cisplatin Plus Etoposide With or Without Bevacizumab as First-Line Treatment in Extensive-Disease Small-Cell Lung Cancer: The GOIRC-AIFA FARM6PMFJM Trial. [J Clin Oncol. 2017

PAK6-Associated Support Vector Machine Classifier: A New Way to Evaluate Response and Survival of Gastric Cancer Treated by 5-FU/Oxaliplatin Chemotherapy

3noGastric cancer (GC) is the 4th most common human malignant disease and the second-leading cancer-related deaths in the world(DeManzoni et al., 2016). Treatment with 5-fluorouracil/oxaliplatin (5-FU/oxaliplatin) chemotherapy has proven to significantly improve survivalof patients with metastatic GCopenopenSobhani, Navid; Generali, Daniele; Roviello, GiandomenicoSobhani, Navid; Generali, Daniele; Roviello, Giandomenic

Cabozantinib as a second-line treatment option in hepatocellular carcinoma

Introduction: Hepatocellular carcinoma (HCC) is one of the most frequent tumors affecting the gastrointestinal tract and a universal cause of morbidity and mortality. Cabozantinib is a strong multi-inhibitor of receptor tyrosine kinases approved for renal cell carcinoma that could be useful also for the treatment of HCC. Areas covered: This review describes the chemical structure, the pharmacologic properties and current knowledge of the efficacy of cabozantinib in the treatment of HCC based on data available from first phase and later phase clinical trials. The ongoing studies testing cabozantinib, either alone or in combination with other drugs, are also described. Expert opinion: Despite the recent achievements in the use of cabozantinib for patients diagnosed with hepatocellular carcinoma, data are still needed to allow clinicians to make better decisions on how to treat specific patient subgroups.</p

Mutant p53 as an Antigen in Cancer Immunotherapy

The p53 tumor suppressor plays a pivotal role in cancer and infectious disease. Many oncology treatments are now calling on immunotherapy approaches, and scores of studies have investigated the role of p53 antibodies in cancer diagnosis and therapy. This review summarizes the current knowledge from the preliminary evidence that suggests a potential role of p53 as an antigen in the adaptive immune response and as a key monitor of the innate immune system, thereby speculating on the idea that mutant p53 antigens serve as a druggable targets in immunotherapy. Except in a few cases, the vast majority of published work on p53 antibodies in cancer patients use wild-type p53 as the antigen to detect these antibodies and it is unclear whether they can recognize p53 mutants carried by cancer patients at all. We envision that an antibody targeting a specific mutant p53 will be effective therapeutically against a cancer carrying the exact same mutant p53. To corroborate such a possibility, a recent study showed that a T cell receptor-like (TCLR) antibody, initially made for a wild-type antigen, was capable of discriminating between mutant p53 and wild-type p53, specifically killing more cancer cells expressing mutant p53 than wild-type p53 in vitro and inhibiting the tumour growth of mice injected with mutant p53 cancer cells than mice with wild-type p53 cancer cells. Thus, novel antibodies targeting mutant p53, but not the wild-type isoform, should be pursued in preclinical and clinical studies.</p

Predictive and Prognostic Value of Non-Coding RNA in Breast Cancer

For decades since the central dogma, cancer biology research has been focusing on the involvement of genes encoding proteins. It has been not until more recent times that a new molecular class has been discovered, named non-coding RNA (ncRNA), which has been shown to play crucial roles in shaping the activity of cells. An extraordinary number of studies has shown that ncRNAs represent an extensive and prevalent group of RNAs, including both oncogenic or tumor suppressive molecules. Henceforth, various clinical trials involving ncRNAs as extraordinary biomarkers or therapies have started to emerge. In this review, we will focus on the prognostic and diagnostic role of ncRNAs for breast cancer

Current status of androgen receptor-splice variant 7 inhibitor niclosamide in castrate-resistant prostate-cancer

Castrate-Resistant Prostate-Cancer (CRPC) is one of the most common malignancies occurring in men. Unfortunately, even if several recently approved agents clinically improved the outcome of CRPC patients, none of these is curative especially for a splice version of the Androgen Receptor (AR) AR-V7, which is a variant of the receptor constitutively activated and does not require the presence of androgens for the activation AR down-stream pathways. Since high AR-V7 expression is one of the most common features of CRPC, targeting this receptor variant is considered as one of the most promising strategies for treating this disease. Therefore anti-AR-V7 molecules could lead to a potential shift in paradigm in the treatment of CRPC. Niclosamide, an already FDA-approved anti-helminthic drug, was identified as a potent AR-V7 inhibitor in prostate cancer cells. Due to the recent positive preclinical results, niclosamide may be an interesting and novel type of targeted treatments for CRPC. This mini-review outlines the most recent pre- and clinical- data on the current status of niclosamide in the treatment of ARV7-positive CRPC patients

Cell-free DNA integrity for the monitoring of breast cancer: Future perspectives?

Breast cancer (BC) is the most common cancer and the second cause of death in women worldwide. Therapeutic options are increasing, but the response to treatments is not always efficient and the risk of recurrence covers decades. In this perspective, the need to have a proper follow-up for the therapeutic responses and for anticipating recurrence it is urgent in the clinical setting. Liquid biopsy provides the basic principle for a non-invasive method for the routinely monitoring of BC. However, due to the heterogeneity of tumors during onset and progression, the search for tumor DNA mutations of targeted genes in plasma/serum is a limiting factor. A possible approach overtaking this problem comes from the measurement of cell-free DNA integrity, which is an independent factor from the mutational status and theoretically is representative of all tumors. This review summarizes the state-of-the-art of cell-free DNA integrity researches in BC, the controversies and the future perspective