“ Research and clinical trials are mainly focused on synthetic small and large molecule Gal-3 inhibitors. Small synthetic molecules have the potential to be toxic at higher doses, whereas larger molecules don’t tend to bind so well. Research is still progressing into these.
“ Research and clinical trials are mainly focused on synthetic small and large molecule Gal-3 inhibitors. Small synthetic molecules have the potential to be toxic at higher doses, whereas larger molecules don’t tend to bind so well. Research is still progressing into these.
Of particular note, they also reviewed modified citrus pectin (MCP):
Modified citrus pectins (MCP) are produced from citrus pectin by sequential alkali and acidic hydrolytic processes to enhance absorbability. Studies in cell lines and animal models suggested that MCP could be an effective anti-metastatic drug for many cancers [185,186,187,188]. The MCP was shown to inhibit in vitro tumor cell adhesion to endothelium [186] and homotypic aggregation and the formation of metastatic deposits of human breast and prostate carcinoma cells in lungs and bones in xenograft rodent models [185,187].
Recently, Gal3-targeting multifunctional core-shell glyconanoparticles based on the low molecular weight dialdehyde oligomers of citrus pectin (CPDA) have been described [188]. These CPDA-based core-shell nanoparticles have been shown to reduce homotypic cellular aggregation, tumor-endothelial cell interactions, and endothelial tube formation—the significant steps of cancer progression [188].
The great thing about MCP is that it is available cheaply, almost off the shelf, and it is being trialled. Unfortunately I would not expect it to be allowed to progress further exactly for this reason:
MCP is commercially available as a food supplement, and at least two clinical investigations of MCP have been completed so far on prostatic neoplasm (FDA-regulated, NCT01681823, Phase 2) and hypertension (non-regulated, NCT01960946). The former study of MCP on prostatic neoplasm assessed its effect on prostate-specific antigen (PSA) kinetics in biochemically relapsed prostate cancer with serial increases in PSA. Moreover, Massachusetts General Hospital (MGH) initiated a Phase 3 randomized, double-blind clinical trial of MCP on knee osteoarthritis (n = 50) (NCT02800629), but the recruitment status is “unknown” on clinicaltrials.gov (accessed on 20 February 2023).
Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis.
…Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months.
…After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.
An ear the end with therapeutics
“ Research and clinical trials are mainly focused on synthetic small and large molecule Gal-3 inhibitors. Small synthetic molecules have the potential to be toxic at higher doses, whereas larger molecules don’t tend to bind so well. Research is still progressing into these.
Of particular note, they also reviewed modified citrus pectin (MCP):
Modified citrus pectins (MCP) are produced from citrus pectin by sequential alkali and acidic hydrolytic processes to enhance absorbability. Studies in cell lines and animal models suggested that MCP could be an effective anti-metastatic drug for many cancers [185,186,187,188]. The MCP was shown to inhibit in vitro tumor cell adhesion to endothelium [186] and homotypic aggregation and the formation of metastatic deposits of human breast and prostate carcinoma cells in lungs and bones in xenograft rodent models [185,187].
Recently, Gal3-targeting multifunctional core-shell glyconanoparticles based on the low molecular weight dialdehyde oligomers of citrus pectin (CPDA) have been described [188]. These CPDA-based core-shell nanoparticles have been shown to reduce homotypic cellular aggregation, tumor-endothelial cell interactions, and endothelial tube formation—the significant steps of cancer progression [188].
The great thing about MCP is that it is available cheaply, almost off the shelf, and it is being trialled. Unfortunately I would not expect it to be allowed to progress further exactly for this reason:
MCP is commercially available as a food supplement, and at least two clinical investigations of MCP have been completed so far on prostatic neoplasm (FDA-regulated, NCT01681823, Phase 2) and hypertension (non-regulated, NCT01960946). The former study of MCP on prostatic neoplasm assessed its effect on prostate-specific antigen (PSA) kinetics in biochemically relapsed prostate cancer with serial increases in PSA. Moreover, Massachusetts General Hospital (MGH) initiated a Phase 3 randomized, double-blind clinical trial of MCP on knee osteoarthritis (n = 50) (NCT02800629), but the recruitment status is “unknown” on clinicaltrials.gov (accessed on 20 February 2023).
Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis.
…Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months.
…After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.
Keywords: PSA doubling time; PectaSol; modified citrus pectin; non-metastatic biochemically relapsed prostate cancer.”
From: “Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Results of a Prospective Phase II Study” (2021)
https://pubmed.ncbi.nlm.nih.gov/34959847/