An innovative technique for preventing telomere elongation and its associated immortalization of cancer cells

Brenda Laster, Carol Isaacson, Ekaterina Perets, Maha Msamra, Esther Priel, John Kalef-Ezra, Joseph Kost

Research output: Contribution to journalMeeting Abstractpeer-review


This work offers an innovative technique to inhibit the activation of the telomerase enzyme over the long term and improve the outcome of cancer treatments. Telomerase activation elongates telomeres, sequences of DNA at the ends of chromosomes. This action confers unlimited proliferation on cancer cells and increases their resistance to chemo- and radio- therapy. Telomeres also lengthen when cells undergo homologous recombination via an Alternative Lengthening of Telomeres (ALT) pathway. Our technique embodies an effective drug delivery system (DDS) that maximizes tumor uptake of the inhibitor and provides its long term continuous release. This is accomplished by the direct, intratumoral insertion of a biodegradable polymeric rod incorporating a telomerase-inhibiting drug. Long-term continuous release of the drug is critical because, if the inhibitor is cleared from the tumor cell, telomerase is rapidly reactivated and the telomeres re-lengthen. The drug is a well-documented telomerase-inhibiting porphyrin (TMPyP4) that is incorporated into a Poly(Lactic-co-Glycolic) Acid (PLGA) polymer and inserted directly into anatomically-accessible tumors. The properties of TMPyP4 are retained even when the porphyrin is tagged with a stable palladium atom (Pd), PdTMPyP4. The molecule binds to, and influences the configuration of G-quadruplex (GQ) regions in DNA. GQs are located, among other sites, in the promoter region of the c-myc oncogene and in the telomeres. By stabilizing the promoter region of c-myc, PdTMPyP4 prevents its over-expression and stimulation of the human telomerase reverse transcriptase (hTERT), a subunit of telomerase, thereby inhibiting the activation of telomerase. The intratumoral insertion of the rod increases tumor-loading of the drug and permits the gradual and continuous release of PdTMPyP4 over the long term.
Original languageEnglish
JournalClinical Cancer Research
StatePublished - 15 Feb 2015


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