Our data suggest that inhibition of hTERT expression by siRNA may constitute a valid strategy of chemosensitization. Future investigation will reveal whether hTERT-specific siRNAs with improved in vivo pharmacokinetics may enter the clinics. Intriguingly, there are a number of drugs used in experimental chemotherapy that are able to downmodulate hTERT expression at the mRNA or protein levels. This applies to rapamycin (Zhou et al., 2003), histone deacetylase inhibitors (Wu et al., 2005), imatinib mesylate (Gleevec) (Uziel et al., 2005), the Bcl-2/Bcl-XL-specific antisense oligonucleotide 4625 (Del Bufalo et al., 2005), as well as vitamin D3 (Jiang et al., 2004). It remains to be determined, however, to which extent hTERT downmodulation may explain the cytotoxic and chemosensitizing effects of such drugs.
Irrespective of these incognita, it appears that hTERT may constitute an ideal target for a double-hit anticancer strategy. Whereas inhibition of the catalytic telomerase activity should limit the lifespan of tumor cells and hence exert a long-term effect obtained by chronic therapy, acute inhibition of the second antiapoptotic function can yield an immediate chemosensitizing effect, including in tumors in which the p53 pathway is subverted. However, tumors in which the Bax-dependent mitochondrial pathway of apoptosis induction has been invalidated by loss of expression of Bax or overexpression of Bcl-2 are refractory to chemosensitization by hTERT inhibition.
Top of pageMaterials and methods
Recent GERN News
- Geron Corporation Reports Second Quarter 2024 Financial Results and Business Highlights • Business Wire • 08/08/2024 11:00:00 AM
- Geron Announces Updated NCCN Guidelines® Recommending RYTELO™ (imetelstat) for the Treatment of Symptomatic Anemia in Patients with Lower-Risk MDS • Business Wire • 07/26/2024 11:30:00 AM
- Geron Corporation Announces Chief Commercial Officer to Depart at End of August 2024 • Business Wire • 07/23/2024 08:15:00 PM
- Geron to Announce Second Quarter 2024 Financial Results on August 8, 2024 • Business Wire • 07/18/2024 08:30:00 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 07/10/2024 08:05:04 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 07/08/2024 07:44:18 PM
- Geron Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) • Business Wire • 06/20/2024 08:30:00 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/12/2024 08:05:08 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/12/2024 08:05:04 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 06/10/2024 09:53:19 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 06/10/2024 04:30:13 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:08 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:06 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:06 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:05 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:03 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:03 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 06/07/2024 08:03:44 PM
- Geron Announces FDA Approval of RYTELO™ (imetelstat), a First-in-Class Telomerase Inhibitor, for the Treatment of Adult Patients with Lower-Risk MDS with Transfusion-Dependent Anemia • Business Wire • 06/07/2024 01:58:00 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/05/2024 08:05:20 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 06/04/2024 09:02:18 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 05/17/2024 08:05:30 PM
- Geron Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) • Business Wire • 05/16/2024 08:30:00 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 05/15/2024 08:07:34 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/13/2024 08:05:15 PM
HealthLynked Corp. Announces Second Quarter and First Half 2024 Results: Continued Cost Reductions Set the Stage for Strategic Shift to App-Based Technology Services • HLYK • Aug 16, 2024 8:00 AM
PickleJar Announces Official Name Change and New Ticker Symbol • NREG • Aug 15, 2024 2:23 PM
VAYK's Q2 Profit Added to Accumulated Net Profit of Over $2.2 Million In 18 Months • VAYK • Aug 15, 2024 9:07 AM
Swifty Global Reports Strong Q2 Performance and Prepares for Major Exchange Uplisting • DRCR • Aug 15, 2024 9:04 AM
Mayback's Global Entertainment Signs Global Distribution Agreement with Children's Media Studio • AHRO • Aug 15, 2024 8:45 AM
POET Technologies Reports Second Quarter 2024 Financial Results • POET • Aug 15, 2024 8:04 AM