NP/CIPN Cancer Research Results

NP/CIPN, neuropathy: Click to Expand ⟱
Source:
Type:

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling adverse effect of some widely used anticancer agents, including taxanes, vinca alkaloids, platinum salts, epothilones, and thalidomide.
Scientific Papers found: Click to Expand⟱
5315- ALC,    Randomized Double-Blind Placebo-Controlled Trial of Acetyl-L-Carnitine for the Prevention of Taxane-Induced Neuropathy in Women Undergoing Adjuvant Breast Cancer Therapy
- Trial, BC, NA
other↑, Serum carnitine level increased with ALC but remained stable with placebo
NP/CIPN↑, This is the first study to our knowledge showing that a nutritional supplement increased CIPN. Patients should be discouraged from using supplements without proven efficacy.

5316- ALC,    Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine
- Trial, BC, NA
NP/CIPN↑, Acetyl-L-carnitine (ALC) was unexpectedly found to increase CIPN in a randomized trial

6681- DCA,    Dichloroacetate (DCA) in Cancer Care
PDK1↓, Specifically, it inhibits pyruvate dehydrogenase kinase, which may convert metabolism from fermentative glycolysis back to oxidative phosphorylation.
Apoptosis↑, This process may induce cancer cell apoptosis through several mechanisms including increased oxidative stress and reduced lactate levels.
ROS↑,
lactateProd↓,
Dose↝, DCA can be administered orally or intravenously.
eff↝, overall, there is insufficient evidence to support the efficacy of DCA as a cancer treatment.
toxicity↓, most studies have found DCA to be reasonably safe and well tolerated, The most common side effect is reversible peripheral neuropathy.
NP/CIPN↑, One of the five patients who entered the trial with some degree of peripheral neuropathy developed a score of 3 in the Total Neuropathy Score (TNS), but this resolved within six months after DCA cessation
Dose↝, doses range from 10-50mg/kg daily, with the most common oral dosing being 6.25-12.5mg/kg taken twice daily.
*BioAv↑, DCA is a small water soluble molecule of 150 Da, allowing it to achieve 100% bioavailability when given either orally or intravenously
*Half-Life↓, Serum DCA levels rise rapidly after oral administration and exhibit a relatively short half-life. elimination half-life of 92 minutes
GSTZ1↝, DCA metabolism is affected by glutathione transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI) genotype status. Individuals with at least one wild-type haplotype metabolize DCA more rapidly and thus may be able to tolerate a higher dose
Glycolysis↓, DCA acts on the mitochondrial matrix of cancer cells, diverting metabolism from fermentative glycolysis back to oxidative phosphorylation
OXPHOS↑,
MPT↑, reopening of voltage and redox sensitive mitochondrial transition pores (22). This allows for the pro-apoptotic mediators, cytochrome c and apoptosis-inducing-factor, to be released into the cytoplasm,
Cyt‑c↑,
AIF↑,
Casp↑, increasing the levels of pro-apoptotic ROS through the activation of caspases
CSCs↓, Although less well established, there is some evidence that DCA may be able to reduce stemness and induce differentiation in cancer stem cells
Remission↑, rigorous treatment cycle with DCA, alpha lipoic acid, and B vitamins and achieved complete remission of his cancer as evidenced by PET scans, CT scans, and laboratory testing. Four years later, the patient remained cancer free.
ChemoSen↑, Several preclinical studies have demonstratedsynergistic effects of DCA with chemotherapeutic agents, including carboplatin (34, 57), oxaliplatin (34, 57), 5-fluorouracil (29), paclitaxel (58, 59), doxorubicin (60), elesclomol (24), and sorafenib (6
RadioS↑, There is preliminary preclinical evidence that DCA may act as a radiosensitizer primarily by increasing levels of reactive oxygen species in tumour cells
toxicity↑, Combined with artesunate one patient experienced fatal liver and bone marrow toxicity.

6679- DCA,    GSTZ1 genotypes correlate with dichloroacetate pharmacokinetics and chronic side effects in multiple myeloma patients in a pilot phase 2 clinical trial
- Trial, Melanoma, NA
PDK1↓, Dichloroacetate (DCA) is an investigational drug targeting the glycolytic hallmark of cancer by inhibiting pyruvate dehydrogenase kinases (PDK).
Half-Life↝, The initial half‐life of DCA was shorter in two patients, correlating with heterozygosity for GSTZ1*A genotype, a high enzyme activity variant.
eff↑, Over 3 months, one patient maintained DCA trough concentrations approximately threefold higher than other patients, which correlated with a low activity promoter genotype (−1002A, rs7160195) for GSTZ1.
NP/CIPN↑, This patient displayed the strongest response, but also the strongest neuropathy.
Dose↝, single oral dose of 25 mg/kg taken at approximately 9 am.
Half-Life↝, DCA was then cleared with a mean half‐life of 93 min (Table 2), with 90% of the drug being cleared by 6 hours, and DCA being undetectable at 24 hours


Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

GSTZ1↝, 1,   OXPHOS↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↑, 1,   MPT↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Glycolysis↓, 1,   lactateProd↓, 1,   PDK1↓, 2,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,   Casp↑, 1,   Cyt‑c↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CSCs↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   Dose↝, 3,   eff↑, 1,   eff↝, 1,   Half-Life↝, 2,   RadioS↑, 1,  

Functional Outcomes(tgid=23) ⓘ

NP/CIPN↑, 4,   Remission↑, 1,   toxicity↓, 1,   toxicity↑, 1,  
Total Targets: 23

Pathway results for Effect on Normal Cells:


Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   Half-Life↓, 1,  
Total Targets: 2

Scientific Paper Hit Count for: NP/CIPN, neuropathy
2 Acetyl-l-carnitine
2 Dichloroacetate
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:1438  State#:%  Dir#:2
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