Arbaclofen placarbil: Difference between revisions

Arbaclofen placarbil
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Revision as of 19:36, 11 February 2025

Overview of antineoplastic resistance

Antineoplastic resistance refers to the ability of cancer cells to resist the effects of antineoplastic agents, which are drugs used to treat cancer. This resistance can be either intrinsic or acquired and poses a significant challenge in the effective treatment of cancer.

Mechanisms of Resistance

Cancer cells can develop resistance to antineoplastic agents through various mechanisms:

Drug Efflux

One of the primary mechanisms is the increased efflux of drugs from cancer cells. This is often mediated by ATP-binding cassette transporters such as P-glycoprotein, which pump the drugs out of the cells, reducing their intracellular concentration and effectiveness.

Drug Inactivation

Cancer cells may also develop the ability to inactivate drugs. This can occur through the increased expression of enzymes that metabolize and neutralize the drugs, such as glutathione S-transferase.

Target Alteration

Changes in the drug target can also lead to resistance. Mutations in the target proteins can reduce the binding affinity of the drugs, rendering them less effective. For example, mutations in the epidermal growth factor receptor (EGFR) can lead to resistance to EGFR inhibitors.

DNA Repair

Enhanced DNA repair mechanisms can allow cancer cells to survive despite the DNA damage caused by certain antineoplastic agents. Overexpression of DNA repair proteins can contribute to this form of resistance.

Cell Death Inhibition

Cancer cells can evade apoptosis, the programmed cell death that is often triggered by antineoplastic agents. Alterations in apoptotic pathways, such as overexpression of anti-apoptotic proteins like Bcl-2, can lead to resistance.

Clinical Implications

Antineoplastic resistance is a major obstacle in cancer treatment, leading to treatment failure and disease progression. Understanding the mechanisms of resistance is crucial for developing strategies to overcome it, such as combination therapies that target multiple pathways or the development of new drugs that can bypass resistance mechanisms.

Strategies to Overcome Resistance

Several strategies are being explored to overcome antineoplastic resistance:

Combination Therapy: Using multiple drugs with different mechanisms of action can help prevent or overcome resistance.
Targeted Therapy: Developing drugs that specifically target resistance mechanisms or mutated proteins.
Biomarker Identification: Identifying biomarkers that predict resistance can help tailor treatments to individual patients.
Novel Drug Delivery Systems: Utilizing nanoparticles or other delivery systems to enhance drug accumulation in cancer cells.

Related pages

Gallery

Diagram illustrating mechanisms of antineoplastic resistance.

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-'''Arbaclofen Placarbil''' (also known as '''AP''') is a prodrug of [[R-baclofen]]. It is designed to improve the pharmacokinetic profile of [[baclofen]] by utilizing a transport pathway to deliver more consistent and prolonged exposure.
+{{Short description|Overview of antineoplastic resistance}}
+{{Drugbox}}
-==Pharmacology==
+'''Antineoplastic resistance''' refers to the ability of cancer cells to resist the effects of [[antineoplastic agents]], which are drugs used to treat [[cancer]]. This resistance can be either intrinsic or acquired and poses a significant challenge in the effective treatment of cancer.
-Arbaclofen Placarbil is a prodrug of R-baclofen, meaning it is metabolized in the body to produce R-baclofen. R-baclofen is the active compound that exerts the therapeutic effects. It acts as a selective agonist for the [[GABA]]B receptors, which are found in the central nervous system. This action results in decreased neuronal excitability, which can help to manage symptoms in a variety of neurological conditions.
-==Clinical Uses==
+==Mechanisms of Resistance==
-Arbaclofen Placarbil has been investigated for use in several conditions, including [[spasticity]] related to multiple sclerosis, [[alcohol dependence]], and [[gastroesophageal reflux disease]] (GERD). However, its most notable application is in the treatment of [[fragile X syndrome]], a genetic disorder that causes a range of developmental problems and cognitive impairment.
+Cancer cells can develop resistance to antineoplastic agents through various mechanisms:
-==Development and Approval==
+===Drug Efflux===
-Arbaclofen Placarbil was developed by [[XenoPort]], a biopharmaceutical company based in Santa Clara, California. The drug was granted Orphan Drug Designation by the [[Food and Drug Administration]] (FDA) for the treatment of fragile X syndrome. However, in 2013, XenoPort announced that it would not continue the development of Arbaclofen Placarbil due to negative results in phase III clinical trials.
+One of the primary mechanisms is the increased efflux of drugs from cancer cells. This is often mediated by [[ATP-binding cassette transporters]] such as [[P-glycoprotein]], which pump the drugs out of the cells, reducing their intracellular concentration and effectiveness.
-==See Also==
+===Drug Inactivation===
-* [[Baclofen]]
+Cancer cells may also develop the ability to inactivate drugs. This can occur through the increased expression of enzymes that metabolize and neutralize the drugs, such as [[glutathione S-transferase]].
-* [[Fragile X syndrome]]
-* [[GABA]]
-* [[Orphan drug]]
+===Target Alteration===
+Changes in the drug target can also lead to resistance. Mutations in the target proteins can reduce the binding affinity of the drugs, rendering them less effective. For example, mutations in the [[epidermal growth factor receptor]] (EGFR) can lead to resistance to EGFR inhibitors.
+===DNA Repair===
+Enhanced DNA repair mechanisms can allow cancer cells to survive despite the DNA damage caused by certain antineoplastic agents. Overexpression of DNA repair proteins can contribute to this form of resistance.
+===Cell Death Inhibition===
+Cancer cells can evade apoptosis, the programmed cell death that is often triggered by antineoplastic agents. Alterations in apoptotic pathways, such as overexpression of anti-apoptotic proteins like [[Bcl-2]], can lead to resistance.
+==Clinical Implications==
+Antineoplastic resistance is a major obstacle in cancer treatment, leading to treatment failure and disease progression. Understanding the mechanisms of resistance is crucial for developing strategies to overcome it, such as combination therapies that target multiple pathways or the development of new drugs that can bypass resistance mechanisms.
+==Strategies to Overcome Resistance==
+Several strategies are being explored to overcome antineoplastic resistance:
+* '''Combination Therapy''': Using multiple drugs with different mechanisms of action can help prevent or overcome resistance.
+* '''Targeted Therapy''': Developing drugs that specifically target resistance mechanisms or mutated proteins.
+* '''Biomarker Identification''': Identifying biomarkers that predict resistance can help tailor treatments to individual patients.
+* '''Novel Drug Delivery Systems''': Utilizing nanoparticles or other delivery systems to enhance drug accumulation in cancer cells.
+==Related pages==
+* [[Chemotherapy]]
+* [[Cancer treatment]]
+* [[Drug resistance]]
+* [[Targeted therapy]]
+==Gallery==
+<gallery>
+File:Antineoplastic_resistances.png|Diagram illustrating mechanisms of antineoplastic resistance.
+</gallery>
+[[Category:Oncology]]
 [[Category:Pharmacology]]
-[[Category:Drugs]]
+[[Category:Cancer treatments]]
-[[Category:Neurology]]
-{{pharma-stub}}