Abstract
Cytotoxic ribonucleases (RNases), such as ranpiranase, represent a novel mechanism-based approach to anticancer therapy. These relatively small proteins selectively attack malignant cells, triggering apoptotic response and inhibiting protein synthesis. Ranpirnase, originally isolated from oocytes of Rana pipiens, is a member of a family of endoribonucleases. The anticancer effects of ranpiranase have been documented in both in vitro and in vivo experimental tumor models. The effects of ranpiranase appear to be selective for cancer cells. Based on Phase I study data, the maximum tolerated dose (MTD) was 960 μg/m2, with the dose-limiting toxicity (DLT) characterized by proteinuria with or without azotemia, peripheral edema, and fatigue. Ranpirnase did not induce myelosuppression, mucositis, alopecia, cardiotoxicity, coagulopathy, hepatotoxicity, or adverse metabolic effects. Phase II tumor-specific trials investigated the activity of ranpirnase in malignant mesothelioma, breast cancer, non-small cell lung cancer, and renal cell cancer. A Phase III randomized study in malignant mesothelioma patients compares the combination of ranpirnase plus doxorubicin to doxorubicin monotherapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 643-650 |
| Number of pages | 8 |
| Journal | Cancer Investigation |
| Volume | 23 |
| Issue number | 7 |
| DOIs | |
| State | Published - 2005 |
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Keywords
- Anticancer therapy
- Ranpiranase
- Ribonucleases
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Ribonucleases as a novel pro-apoptotic anticancer strategy : Review of the preclinical and clinical data for ranpirnase. / Costanzi, John; Sidransky, David; Navon, Ami; Goldsweig, Howard.
In: Cancer Investigation, Vol. 23, No. 7, 2005, p. 643-650.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ribonucleases as a novel pro-apoptotic anticancer strategy
T2 - Review of the preclinical and clinical data for ranpirnase
AU - Costanzi, John
AU - Sidransky, David
AU - Navon, Ami
AU - Goldsweig, Howard
PY - 2005
Y1 - 2005
N2 - Cytotoxic ribonucleases (RNases), such as ranpiranase, represent a novel mechanism-based approach to anticancer therapy. These relatively small proteins selectively attack malignant cells, triggering apoptotic response and inhibiting protein synthesis. Ranpirnase, originally isolated from oocytes of Rana pipiens, is a member of a family of endoribonucleases. The anticancer effects of ranpiranase have been documented in both in vitro and in vivo experimental tumor models. The effects of ranpiranase appear to be selective for cancer cells. Based on Phase I study data, the maximum tolerated dose (MTD) was 960 μg/m2, with the dose-limiting toxicity (DLT) characterized by proteinuria with or without azotemia, peripheral edema, and fatigue. Ranpirnase did not induce myelosuppression, mucositis, alopecia, cardiotoxicity, coagulopathy, hepatotoxicity, or adverse metabolic effects. Phase II tumor-specific trials investigated the activity of ranpirnase in malignant mesothelioma, breast cancer, non-small cell lung cancer, and renal cell cancer. A Phase III randomized study in malignant mesothelioma patients compares the combination of ranpirnase plus doxorubicin to doxorubicin monotherapy.
AB - Cytotoxic ribonucleases (RNases), such as ranpiranase, represent a novel mechanism-based approach to anticancer therapy. These relatively small proteins selectively attack malignant cells, triggering apoptotic response and inhibiting protein synthesis. Ranpirnase, originally isolated from oocytes of Rana pipiens, is a member of a family of endoribonucleases. The anticancer effects of ranpiranase have been documented in both in vitro and in vivo experimental tumor models. The effects of ranpiranase appear to be selective for cancer cells. Based on Phase I study data, the maximum tolerated dose (MTD) was 960 μg/m2, with the dose-limiting toxicity (DLT) characterized by proteinuria with or without azotemia, peripheral edema, and fatigue. Ranpirnase did not induce myelosuppression, mucositis, alopecia, cardiotoxicity, coagulopathy, hepatotoxicity, or adverse metabolic effects. Phase II tumor-specific trials investigated the activity of ranpirnase in malignant mesothelioma, breast cancer, non-small cell lung cancer, and renal cell cancer. A Phase III randomized study in malignant mesothelioma patients compares the combination of ranpirnase plus doxorubicin to doxorubicin monotherapy.
KW - Anticancer therapy
KW - Ranpiranase
KW - Ribonucleases
UR - http://www.scopus.com/inward/record.url?scp=33344475705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33344475705&partnerID=8YFLogxK
U2 - 10.1080/07357900500283143
DO - 10.1080/07357900500283143
M3 - Article
C2 - 16305992
AN - SCOPUS:33344475705
VL - 23
SP - 643
EP - 650
JO - Cancer Investigation
JF - Cancer Investigation
SN - 0735-7907
IS - 7
ER -