1,721,102 research outputs found
The oral tyrosine kinase inhibitors lapatinib and sunitinib: new opportunities for the treatment of brain metastases from breast cancer?
No full textCombining temozolomide with other antitumor drugs and target-based agents in the treatment of brain metastases: an unending quest or chasing a chimera?
No full textINTRODUCTION: Medical treatment of brain metastases (BM) is still a controversial issue in cancer therapy being mainly limited by the existence of the BBB. Temozolomide (TMZ) can cross BBB and several clinical trials have been performed attempting to demonstrate the activity of TMZ in combination with whole brain radiotherapy (WBRT) in the treatment of BM. AREAS COVERED: This review summarizes TMZ-WBRT combination trials highlighting the confounding factors that limit the interpretation of the achieved results and describes the main clinical trials using TMZ in combination with other cytotoxic or biological agents. The main limitations of these trials are: i) patient selection for heterogenous primitive neoplasms and for heterogeneous neuro-functional score; ii) poor penetration across BBB of the other drugs; iii) cumulative toxicity and iv) poor control of extracranial tumor sites. EXPERT OPINION: Biotechnological, biological and biochemical advances in the management of BM could allow in short time the definition of new schedules based on the rational use of new anticancer weapons. The latter could be cytotoxic agents encapsulated in nanotechnological tools able to cross BBB, lipophilic small kinase inhibitors (lapatinib, sunitinib), mTOR inhibitors and PARP inhibitors combined with old drugs such as TMZ
Design, Synthesis and Evaluation. Int J Mol Sci. 2025 Jun 25;26(13):6090
No full textAmong the fundamental pathological processes, tumorigenesis is arguably the most complex. It results from the accumulation of genetic alterations that typically unfold over many years, leading to the gradual breakdown of homeostatic barriers at the cellular, tissue, and ultimately organismal levels. Over the past few decades, discoveries on the molecular and cellular mechanisms of tumorigenesis have had, and continue to have, a profound impact on anticancer pharmacotherapy. It is noteworthy that since the early 2000s, the number of anticancer drugs approved for clinical use has increased from a few dozen [1] to several hundred distinct agents [2]. With the aim of targeting the hallmarks of tumorigenesis [3]—the functional traits that enable cancer cells to survive, proliferate, and disseminate—numerous classes of anticancer drugs are currently under active investigation and development. This Special Issue on “New Anticancer Agents: Design, Synthesis and Evaluation” brings together experimental studies and review articles that, at least in part, reflect the complexity of this disease and highlight several aspects of basic research aimed at therapeutic innovation
Chemotherapy in the management of brain metastases: the emerging role of fotemustine for patients with melanoma and NSCLC.
No full textTwo faces for Janus: recombinant human erythropoiesis-stimulating agents and cancer mortality.
No full textUntreated anemia in cancer patients has severe consequences for many organ systems. Erythropoiesis-stimulating agents (ESAs) are indicated for the treatment of chemotherapy-induced anemia in cancer patients. Several studies in patients with solid tumors have shown that these agents effectively increase hemoglobin levels, improve the quality of life and reduce the requirement for emergency blood transfusions, regardless of the type of concomitantly administered chemotherapy. The meta-analysis evaluates the impact of ESAs during the active study period on mortality and the overall survival during the longest available follow-up, irrespective of anticancer treatment, with little heterogeneity between trials. A total of 10,441 patients on chemotherapy were enrolled in 38 trials. There was little evidence for a difference between trials of patients administered different anticancer treatments (p for interaction = 0.42). The meta-analysis demonstrated that ESAs increased mortality by 17% during the active study periods and worsened overall survival in patients with cancer. However, 62% of patients evaluated in this analysis started the ESA therapy with basal hemoglobin values over that recommended by ASCO/ASH guidelines. However, the high quality of meta-analysis and the novelty of the information do not represent an obstacle for the continued the use of ESAs within the revised European Organisation for Research and Treatment of Cancer (EORTC) guidelines and the revised labels
Latest developments in targeted therapy for hepatocellular carcinoma.
No full textThe advent of sorafenib can be considered as a turning point in the history of advanced hepatocellular carcinoma. After unfortunate attempts at using chemotherapy, drugs targeting key pathways have generated new perspectives in this field. This means not only killing both tumor cells and cirrhotic fragile tissue, but killing them selectively; more than was previously possible. This seems like the Copernican Revolution. However, hepatocellular carcinoma is pathogenetically complicated, resulting from the number of mutations. Until now, there has not been a single drug able to block and reverse abnormally activated signaling in hepatocellular carcinoma cells. In this article, we describe the most promising targeted drugs being studied in hepatocellular carcinoma and depict the possible future scenarios
Erlotinib: early clinical development in brain cancer.
No full textGlioblastoma (GBM) is the most common brain cancer in adults. It is also, unfortunately, the most aggressive type and the least responsive to therapy. Overexpression of EGFR and/or EGFRvIII is frequently found in GBM and is frequently associated with the more malignant phenotype of the disease and a poor clinical outcome. EGFR-targeted therapy represents a promising anti-GBM therapy. Two EGFR kinase inhibitors, gefitinib and erlotinib have been tested in clinical trials for malignant gliomas. However, the clinical efficacy of EGFR-targeted therapy has been only modest in GBM patients.
AREAS COVERED:
The authors provide an evaluation of erlotinib as a potential therapy for GBM. The authors highlight experiences drawn from clinical trials and discuss the challenges, which include the insufficient penetration through the blood-brain barrier (BBB) and chemoresistance.
EXPERT OPINION:
Malignant brain tumours have a very complex signalling network that is not only driven by EGFR. This complexity dictates tumour sensitivity to EGFR-targeted therapies. Alternative kinase signalling pathways may be involved in parallel with the inhibited target, so that a single target's inactivation is not sufficient to block downstream oncogenic signalling. The use of nanocarriers offers many opportunities, such as the release of the drug to specific cells or tissues, together with the ability to overcome different biological barriers, like the BBB
ASCO 2013: Bevacizumab and glioblastoma-a marriage dissolution?
No full textThe prognosis of patients affected by glioblastoma (GBM) is grim albeit the integrated therapeutic approaches now available. Standard surgery followed by chemoradiation median overall survival (OS) reaches 15 months in clinical trials. Despite primary treatment, recurrence is the rule in patients with GBM and for them OS ranges from 6 to 9 months. In recent years, the therapeutic scenario has been profoundly changed in view of the promising results obtained by bevacizumab (Avastin* *Avastin is a registered trade name of Bevacizumab, F. Hoffmann-La Roche Ltd, Basel, Switzerland.), the most promising anti-angiogenesis agent, in two clinical trials. The results of both trials were presented at the last ASCO meeting in Chicago. Progression free survival was significantly improved with an acceptable safety and tolerability profile but surprisingly quality of life was preserved only in the AVAGlio trial. However, both studies showed that overall survival was not improved adding bevacizumab to temozolomide and radiotherapy. © 2014 Informa UK Ltd.The prognosis of patients affected by glioblastoma (GBM) is grim albeit the integrated therapeutic approaches now available. Standard surgery followed by chemoradiation median overall survival (OS) reaches 15 months in clinical trials. Despite primary treatment, recurrence is the rule in patients with GBM and for them OS ranges from 6 to 9 months. In recent years, the therapeutic scenario has been profoundly changed in view of the promising results obtained by bevacizumab (Avastin*), the most promising anti-angiogenesis agent, in two clinical trials. The results of both trials were presented at the last ASCO meeting in Chicago. Progression free survival was significantly improved with an acceptable safety and tolerability profile but surprisingly quality of life was preserved only in the AVAGlio trial. However, both studies showed that overall survival was not improved adding bevacizumab to temozolomide and radiotherapy
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