About this Research Topic
It is well established that the factors that determine the pharmacokinetic behavior of a drug include absorption, distribution, metabolism and excretion. All drugs, including anticancer agents, undergo a degree of metabolism when administered to patients.
Specifically, metabolism of potential anti-cancer agents has been reported within major metabolic compartments (hepatic sinusoids and blood stream) but also within tumor tissues/cells themselves. Altogether, these processes affect the pharmacological profile of these drugs. Specifically, the intra-tumoral microenvironment is unique in terms of hypoxia (low pO2), acidity (lowpH) and the presence of several enzymes and cellular transporters (such as P-glycoprotein and related efflux pumps). Today, the detection and modulation of intra-tumoral metabolic pathways/cellular transporters - unique to specific malignant disorders in terms of their distinct intracellular and extracellular niche - are major focuses in biomedical and pharmaceutical research.
There are several specific areas that are currently under investigation as potential therapeutic targets to improve the pharmacokinetic properties of anti-solid tumor drugs. These include intra-tumoral proteolytic activity with consequent degradation of peptide/antibody-based drugs; intra-tumoral overexpression of transporters with consequent anticancer drug efflux; intra-tumoral hypoxia with consequent activation/inactivation of chemotherapeutic drugs; and endosomal sequestration with consequent inactivation of acid sensitive chemotherapeutics.
As mortality rates due to neoplastic diseases have remained constant over the past 50 years, a clear conceptual twist in the way we are thinking about fighting cancer is needed to tackle this disease. Targeting specific intra-tumoral drug metabolism processes or utilising metabolic pathways to increase drugs bioavailability could constitute novel anticancer treatment approaches. Concepts like metronomic therapy (fractionated dosing) and tumor priming (small pre-dosing) with consequent enhancement of intra-tumoral drug perfusion/concentration/entrapment of anti-cancer drugs represent this new conceptual twist of fighting solid tumors.
In this Research Topic, manuscripts (Review as well Original Research articles) addressing intra-tumoral, as well as intracellular pharmacokinetic and metabolic profiling for anticancer drugs, are highly encouraged. Investigations related to metronomic therapy, solid tumor priming and overcoming pharmacokinetic hurdles with novel drug delivery systems are of special consideration in the current issue.
Subtopics that are welcome, but not limited to:
• Modulation of the anti-cancer drug metabolic pathways for improved anti-tumor pharmacological response,
• Anti-cancer drug metabolic pathways’ utilization for the enhancement of drug bioavailability
• Targeting intra-tumoral transporter to improve cellular pharmacokinetics and intra-cellular accumulation of chemotherapeutics
Keywords: Solid tumor, pharmacokinetics, apoptosis, autophagy, bioavailability
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