Tumor Regression of Advanced Carcinomas Following Intra-and/or Peri-Tumoral Inoculation with VRCTC-310 in Humans: Preliminary Report of Two Cases

Abstract

The authors report their clinical experience with VRCTC-310 in two patients suffering with advanced cancer in which the skin was severely compromised. VRCTC-310 is a combination of the snake venoms crotoxin (CT) and cardiotoxin (CD). The local (peritumoral) treatment with the drug (0.O14 mg/kg/week during 6 weeks) provoked the complete disappearance of a relapsed skin squamous cell cancer in one patient. The other patient was an aged woman with local-advanced breast cancer (carcinoma en cuirasse) who was inoculated intra-and-peritumoral with VRCTC-310. After 6 weekly courses (0.014 mg/kg/week) with the drug a > 80% tumor reduction was seen. A 133 days follow-up demonstrated not only an objective complete response of the primary tumor mass, but the disappearance of supraclavicular tumor mass as well a significant reduction in lymphangitis. To our knowledge, this is the first communication about the in vivo antitumoral activity of VRCTC-310 when injected locally to humans. Further studies are now in progress.

Crystal Structure of Crotoxin Reveals Key Residues Involved in the Stability and Toxicity of This Potent Heterodimeric β-Neurotoxin

“…11,12 Numerous studies have shown that the crotoxin heterodimer, as well as its CB subunit, displays a number of other pharmacological effects in addition to neurotoxicity, including local and systemic myotoxicity, necrosis of skeletal muscle, and myoglobinuria. [13][14][15] Moreover, crotoxin exhibits a preferential cytotoxic activity against various types of tumor cells and is more cytotoxic to cell lines that express high levels of epidermal growth factor receptors; [16][17][18][19] accordingly, it is used in the treatment of carcinomas. 20 Anti-inflammatory, immunomodulatory, and analgesic effects of crotoxin have also been reported.…”

Efecto citotóxico de fosfolipasas A2 del veneno de Crotalus durissus cumanensis de Colombia

“…Se ha evaluado el efecto anticancerígeno de diversas toxinas y venenos ofídicos, como fuentes de nuevas moléculas en la lucha contra el cáncer (35)(36)(37)(38)(39). Además, la citotoxicidad de los venenos y las fosfolipasas A2 resulta ser un problema para su futuro uso biomédico.…”

“…Además de su citotoxicidad, el efecto anticancerígeno de estas toxinas podría estar relacionado con autofagia de las células tumorales (40). La escasa toxicidad y la ausencia de neurotoxicidad residual de la crotoxina B en estudios con animales, refuerzan su uso en seres humanos como ya ha sido previamente demostrado (35,36,41).…”

Crotalus durissus terrificus venom as a source of antitumoral agents

“…Although Crtx has been used with some success in the treatment of several patients with squamous skin and breast cancer, to the best of our knowledge, no product derived from CV or its components, such as Crtx, has achieved worldwide application in clinics indicating that further studies should be performed (7,19).…”