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Alanosine (UCSD)
J Yu1
1Scripps Research Institute, Department of Molecular & Experimental Medicine, La Jolla, CA 92037, USA. johnyu@scripps.edu
Abstract:
Researchers at the University of California at San Diego (UCSD) are developing alanosine as a potential treatment for cancer [227466], [408222]. The compound was originally under development in collaboration with Triangle, which initiated its development in 1996 [227466], but later discontinued development of the compound [406677]. As of May 2001, UCSD's ongoing clinical trials of alanosine included phase II trials for non-small cell lung cancer (NSCLC) and phase I trials for acute lymphoid leukemia (ALL), while a phase II trial for glioma at UCSD had been suspended [408222]. Alanosine is an amino acid analog originally derived from Streptomyces alanosinicus. It interferes with the de novo synthesis of adenosine in both malignant and normal cells. In cancer cells that lack methyladenosine phosphorylase (MTAP, required in the salvage pathway), alanosine should deprive such cells (but not normal cells) of de novo synthesized adenosine [277968]. In early 1997, patients were being recruited for a phase II pilot efficacy trial of alanosine as a treatment for glioma and NSCLC, since a significant number of these tumor types lack MTAP and, it was hoped, would therefore be sensitive to alanosine [239280], [248260]. Phase I and II trials were completed in the 1980s by the NCI before they were discontinued because alanosine caused toxicity typically associated with chemotherapy, and did not produce significant response rates in common tumors such as breast or colon cancers. Researchers at UCSD found that some types of cancer lack MTAP, which was responsible for alanosine's previous clinical failure [227466]; phase II trials were being carried out at the university in 1997 [269338]. Triangle obtained an option for a worldwide license from the Regents of the University of California that expired in September 1998 (but had an option to extend the period for a further one year) [277968].
Insights
Alanosine, an amino acid analog, is being investigated by UCSD researchers as a cancer treatment. It targets cancers lacking methyladenosine phosphorylase (MTAP), potentially overcoming previous toxicity and efficacy issues.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Alanosine, an amino acid analog derived from Streptomyces alanosinicus, interferes with adenosine synthesis.
- Previous NCI trials in the 1980s were discontinued due to toxicity and lack of efficacy in common cancers.
- Researchers identified that methyladenosine phosphorylase (MTAP) deficiency in certain cancers could be a key to alanosine's effectiveness.
Purpose of the Study:
- To evaluate alanosine as a potential cancer therapeutic, particularly in tumors lacking MTAP.
- To explore alanosine's efficacy in non-small cell lung cancer (NSCLC) and acute lymphoid leukemia (ALL).
Main Methods:
- Phase II clinical trials for NSCLC and phase I trials for ALL were conducted by UCSD.
- Patient recruitment for phase II trials in glioma and NSCLC occurred in early 1997.
- The mechanism of action involves depriving cancer cells lacking MTAP of de novo synthesized adenosine.
Main Results:
- UCSD is developing alanosine for cancer treatment, focusing on MTAP-deficient tumors.
- Ongoing trials include phase II for NSCLC and phase I for ALL as of May 2001.
- A phase II trial for glioma was suspended.
Conclusions:
- Alanosine shows potential as a targeted cancer therapy for MTAP-deficient malignancies.
- Further clinical trials are necessary to establish alanosine's safety and efficacy profile.
- Understanding MTAP status is crucial for patient selection in alanosine therapy.