Advances in cyclin-dependent kinase inhibitors for the treatment of melanoma.

This article summarizes the rationale for, and development of CDK inhibitors in melanoma, with their evolution from pan-CDK inhibitors to highly specific agents, throughout clinical trials and finally their potential future use. EXPERT OPINION: Whilst CDK inhibitors have been practice changing in breast cancer management, their efficacy is yet to be proven in melanoma. Combination with BRAF/MEK inhibitors has been hindered by dose-limiting toxicities, but their role may yet to be found within the spectrum of biomarker-derived personalized melanoma management. The effect that CDK inhibitors can have as an adjunct to immunotherapy also remains to be seen. PMID: 33030382 [PubMed - as supplied by publisher]
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research

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Basel, 18 September 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Medicines Agency ’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Tecentriq® (atezolizumab) in combination with Avastin® (bevacizumab) for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have not received prior systemi c therapy. Based on this recommendation, a final decision regarding approval of Tecentriq in combination with Avastin in this disease setting, along with the full details of the approved indication, is expe...
Source: Roche Investor Update - Category: Pharmaceuticals Source Type: news
(Johns Hopkins Medicine) Johns Hopkins Medicine researchers have added to evidence that a gene responsible for turning off a cell's natural " suicide " signals may also be the culprit in making breast cancer and melanoma cells resistant to therapies that use the immune system to fight cancer. A summary of the research, conducted with mice and human cells, appeared Aug. 25 in Cell Reports.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
The exploitation of the immune system ’s anti-cancer roles and clinical actionability has opened a new chapter in cancer treatment [1]. Although breast cancer patients are now provided with a variety of therapies, still a fairly high proportion of them experiences resistance or non-responsiveness to pharmacotherapy, including immunoth erapy [2–4]. In this respect, cellular immunotherapy (CI) is emerging as an intriguing field of active research both in translational and clinical settings [5,6]. Despite CI has been initially celebrated in hematologic malignancies and melanoma, several studies have been carried o...
Source: Cancer Treatment Reviews - Category: Cancer & Oncology Authors: Source Type: research
In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues. PMID: 32623581 [PubMed - as supplied by publisher]
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: Clin Transl Oncol Source Type: research
athew Natural killer (NK) cells play a pivotal role in the immune system, especially in the recognition and clearance of cancer cells and infected cells. Their effector function is controlled by a delicate balance between the activating and inhibitory signals. We have identified 2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) as NK cell receptors regulating NK cell cytotoxicity. Lectin-like transcript 1 (LLT1), a member of the C-type lectin-like domain family 2 (CLEC2D), induced IFN-g production but did not directly regulate cytolytic activity. Interestingly, LLT1 expressed on other cells acts as a ligand for an NK cell in...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractPurpose of ReviewNeoadjuvant therapy in melanoma is an area of active investigation with numerous completed and ongoing trials studying a variety of therapeutic interventions utilizing diverse designs. Here, we review completed and ongoing neoadjuvant trials in melanoma, discuss endpoint assessment, and highlight biomarker development in this context.Recent FindingsHigh-risk resectable melanoma with clinically detectable lymph node (LN) with or without in-transit and/or satellite metastases represent ~  20% of melanoma patients and have a high risk of relapse despite definitive surgery. Adjuvant therapy with...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
This study identified specific cfmiRs in MBM plasma samples that may potentially allow for assessment of melanoma patients developing MBM. The cfmiR signatures identified in both blood and urine may have potential utility to assess CII responses after further validation.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Sumoylation is the Posttranslational modification gaining most of the research interest recently. Sumoylation is involved in various crucial functions of the cell such as regulation of cell cycle, DNA damage repair, apoptosis etc. Oncology is advancing in radiotherapy, targeted chemotherapy, various forms of immunotherapy and targeted gene therapy. Researches are being conducted to prove its connotation with a variety of cancers and inhibitors are being developed to obstruct the fatal effect caused by misbalance of the SUMO-catalytic cycle. It has been shown that upregulation of certain enzymes of Sumoyla...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
Lysine specific demethylase 1 (LSD1) is a key epigenetic eraser enzyme implicated in cancer metastases and recurrence. Nuclear LSD1 phosphorylated at serine 111 (nLSD1p) has been shown to be critical for the development of breast cancer stem cells. Here we show that circulating tumor cells isolated from immunotherapy-resistant metastatic melanoma patients express higher levels of nLSD1p compared to responders, which is associated with co-expression of stem-like, mesenchymal genes. Targeting nLSD1p with selective nLSD1 inhibitors better inhibits the stem-like mesenchymal signature than traditional FAD-specific LSD1 catalyti...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractTriple-negative breast cancer constitutes  ~ 15% of all breast cancer subtypes. Because of the negative hormone receptor and human epidermal growth factor receptor 2 status, therapy is mainly based on chemotherapy with a poor median overall survival in the metastatic setting of ~ 18 months. Compared to other breast cancer subtypes, triple-negative breast cancer is characterized by a higher mutational load, which renders the tumor immunogenic and amenable to immunotherapeutic intervention. Based on the promising results of immunotherapy in other cancer entities, including melanoma or...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
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