GTI-2040. Lorus Therapeutics

Curr Opin Investig Drugs. 2001 Oct;2(10):1462-6.


Loris Therapeutics (formerly GeneSense Therapeutics) is developing the antisense oligonucleotide GTI-2040, directed against the R2 component of ribonucleotide reductase, for the potential treatment of cancer [348194]. It is in phase I/II trials [353796] and Lorus had anticipated phase II trials would be initiated in July 2001. By August 2001, GTI-2040 was undergoing a phase II trial as a monotherapy for the potential treatment of renal cell carcinoma, and was about to enter a phase II combination study for this indication with capecitabine (Hoffmann-La Roche). At this time, the company was also planning a phase II trial to study the drug's potential in the treatment of colorectal cancer [418739]. GTI-2040 has been tested in nine different tumor models, including tumors derived from colon, liver, lung, breast, kidney and ovary. Depending on the tumor model, significant inhibition of tumor growth, disease stabilization and dramatic tumor regressions was observed [347683]. Lorus filed an IND to commence phase I/II trials with GTI-2040 in the US in November 1999 [347683], and received approval for the trials in December 1999 [349623]. As of January 2000, these trials had commenced at the University of Chicago Cancer Research Center; it was reported in February 2000 that dosing to date had been well tolerated with no apparent safety concerns [357449]. Lorus has entered into a strategic supply alliance with Proligo to provide the higher volumes of drug product required for the planned multiple phase II trials [385976]. In February 1998, Genesense (now Lorus) received patent WO-09805769. Loris also received a patent (subsequently identified as WO-00047733) from the USPTO in January 2000, entitled 'Antitumor antisense sequences directed against components of ribonucleotide reductase' covering the design and use of unique antisense anticancer drugs, including GTI-2040 and GTI-2501 [353538].

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents / toxicity
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Humans
  • Neoplasms / drug therapy*
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense / adverse effects*
  • Oligonucleotides, Antisense / metabolism
  • Oligonucleotides, Antisense / pharmacology
  • Oligonucleotides, Antisense / therapeutic use*
  • Oligonucleotides, Antisense / toxicity
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense
  • GTI2040