Organoboronic Acids and Esters in Human Cancer Treatment
Yes, organoboronic acids and their esters have been extensively used in humans with cancer, most notably as FDA-approved proteasome inhibitors for multiple myeloma treatment. 1, 2
FDA-Approved Boronic Acid Cancer Drugs
Bortezomib, a modified dipeptidyl boronic acid, is FDA-approved and widely used for treating multiple myeloma and mantle cell lymphoma in humans. 1, 3 This represents the most clinically successful application of organoboronic acid chemistry in oncology, with proven efficacy in both previously untreated and relapsed disease settings. 1
Clinical Evidence in Multiple Myeloma
In previously untreated multiple myeloma patients, bortezomib combined with melphalan and prednisone demonstrated superior outcomes compared to melphalan-prednisone alone, with median overall survival of 56.4 months versus 43.1 months (hazard ratio 0.695,95% CI: 0.57-0.85). 1
The drug showed remarkable efficacy in relapsed multiple myeloma with acceptable toxicity profiles in Japanese phase I/II studies and international trials. 3
Bortezomib functions as a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome, disrupting normal cellular homeostasis and leading to cancer cell death. 1
Mechanism and Drug Development
The boronic acid functional group serves as an electrophilic moiety with high affinity for hydroxyl groups in catalytic sites of proteolytic enzymes, creating reversible covalent bonds with slow dissociation rates. 4
Five boronic acid drugs have been approved by the FDA and Health Canada, with two specifically designed for cancer treatment (both targeting multiple myeloma). 2
Ixazomib citrate represents the first commercially available oral proteasome inhibitor, though it functions as a pseudo-prodrug that rapidly hydrolyzes to its active boronic acid form. 5
Ongoing Development and Research
Novel dipeptide boronic acid ester derivatives are under investigation as slowly-released oral prodrugs with improved stability profiles compared to ixazomib. 5
Boronic acid prodrugs targeting reactive oxygen species within the tumor microenvironment represent an emerging strategy for selective anticancer chemotherapy, with exponential growth in research over the past decade. 6
Current research focuses on six major cancer types: multiple myeloma, prostate cancer, breast cancer, lung cancer, cervical cancer, and colon cancer, with promising preliminary activities requiring further investigation. 2
Clinical Considerations
Maximum proteasome inhibition (70-84%) occurs within 5 minutes of bortezomib administration at therapeutic doses of 1.0-1.3 mg/m². 1
The drug distributes widely to most body tissues including the myocardium, with mean distribution volumes ranging from 498 to 1884 L/m². 1
No dosage adjustment is required for renal impairment (including dialysis patients), though dose reduction is necessary for moderate-to-severe hepatic impairment where exposure increases by approximately 60%. 1