Circulating markers in metastatic cancer: new perspectives

P-glycoprotein, also known as ABCB1 in the ABC transporter family, confers the simultaneous resistance of metastatic cancer cells towards various anticancer drugs with different targets and diverse chemical structures. The exploration of safe and specific inhibitors of this pump has always been the pursuit of scientists for the past four decades. Naturally occurring flavonoids as benzopyrone derivatives were recognized as a class of nontoxic inhibitors of P-gp. The recent advent of synthetic flavonoid dimer FD18, as a potent P-gp modulator in reversing multidrug resistance both in vitro and in vivo, specifically targeted the pseudodimeric structure of the drug transporter and represented a new generation of inhibitors with high transporter binding affinity and low toxicity. This review concerned the recent updates on the structure-activity relationships of flavonoids as P-gp inhibitors, the molecular mechanisms of their action and their ability to overcome P-gp-mediated MDR in preclinical studies. It had crucial implications on the discovery of new drug candidates that modulated the efflux of ABC transporters and also provided some clues for the future development in this promising area.

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Targeting Tumour Metastasis: The Emerging Role of Nanotechnology

Current Medicinal Chemistry ◽

10.2174/0929867326666181220095343 ◽

2020 ◽

Vol 27 (8) ◽

pp. 1367-1381 ◽

Cited By ~ 2

Author(s):

Sarah Visentin ◽

Mirela Sedić ◽

Sandra Kraljević Pavelić ◽

Krešimir Pavelić

Keyword(s):

Cancer Progression ◽

Metastatic Cancer ◽

Treatment Strategies ◽

Metastatic Progression ◽

Therapeutic Concept ◽

Molecular Alterations ◽

Tumour Metastasis ◽

Metastatic Cells ◽

Metastatic Process ◽

Underlying Mechanisms

The metastatic process has still not been completely elucidated, probably due to insufficient knowledge of the underlying mechanisms. Here, we provide an overview of the current findings that shed light on specific molecular alterations associated with metastasis and present novel concepts in the treatment of the metastatic process. In particular, we discuss novel pharmacological approaches in the clinical setting that target metastatic progression. New insights into the process of metastasis allow optimisation and design of new treatment strategies, especially in view of the fact that metastatic cells share common features with stem cells. Nano- and micro-technologies are herein elaborated in details as a promising therapeutic concept in targeted drug delivery for metastatic cancer. Progression in the field could provide a more efficient way to tackle metastasis and thus bring about advancements in the treatment and management of patients with advanced cancer.

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Malignant Pleural Effusion: Still a Long Way to Go

Reviews on Recent Clinical Trials ◽

10.2174/1574887114666181204105208 ◽

2019 ◽

Vol 14 (1) ◽

pp. 24-30 ◽

Cited By ~ 2

Author(s):

Fausto Meriggi

Keyword(s):

Pleural Effusion ◽

Malignant Pleural Effusion ◽

English Language ◽

Metastatic Cancer ◽

Primary Tumour ◽

Clinical Problem ◽

Therapeutic Options ◽

High Morbidity ◽

Sclerosing Agents ◽

Pubmed Database

Background:Malignant pleural effusion, which is a common clinical problem in patients with cancer, may be due to both primary thoracic tumours or to a metastatic spread in the chest and constitutes the first sign of disease in approximately 10% of patients. Almost all cancers can potentially produce a pleural effusion. The presence of malignant tumour cells in the pleural fluid is generally indicative of advanced disease and is associated with high morbidity and mortality with reduced therapeutic options. Dyspnoea during mild physical activity or at rest is generally the typical sign of restrictive respiratory failure. </P><P> Methods: This is a systematic review of all the main articles in the English language on the topic of malignant pleural effusion and reported by the Pubmed database from 1959 to 2018. I reviewed the literature and guidelines with the aims to focus on what is known and on future pathways to follow the diagnosis and treatment of malignant pleural effusions.Results:The main goal of palliation of a malignant pleural effusion is a quick improvement in dyspnoea, while thoracentesis under ultrasound guidance is the treatment of choice for patients with a limited life expectancy or who are not candidates for more invasive procedures such as drainage using an indwelling small pleural catheter, chemical pleurodesis with sclerosing agents, pleurectomy or pleuro-peritoneal shunt.Conclusion:Despite progress in therapeutic options, the prognosis remains severe, and the average survival is 4-9 months from the diagnosis of malignant pleural effusion. Moreover, mortality is higher for patients with malignant pleural effusion compared with those with metastatic cancer but no malignant pleural effusion. Therefore, the prognosis of these patients primarily depends on the underlying disease and the extension of a primary tumour. This review focuses on the most relevant updates in the management of malignant pleural effusion.

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