AI collaboration to optimise development of cancer inhibitor drug 

""

Lantern Pharma has entered a strategic AI-driven collaboration with French biotechnology company Oregon Therapeutics to optimise the development of its first-in-class protein disulfide isomerase (PDI)1inhibitor drug candidate XCE853 in novel and targeted cancer indications.  

Lantern will be leveraging its RADR AI platform to uncover biomarkers and efficacy-associated signatures of XCE853 across solid tumours that can aid in precision development. Collaborative efforts are expected to identify biomarker signatures that can be used to stratify tumours most responsive to XCE853 and guide potential future clinical development and patient selection.  

Oregon Therapeutics is developing XCE853 in various cancer indications, including drug-resistant ovarian and pancreatic cancer, certain haematological cancers and several paediatric cancers including CNS cancers.

PDIs for cancer therapy

PDIs are promising targets for cancer therapy raising clinical interest recently2notably for their potential in cancers of poor prognosis like breast cancer3or ovarian cancer. Up-regulated expression of PDIs was found to be associated with worse clinical outcome in numerous cancers such as hepatocellular carcinoma4, as well as breast and ovarian cancers5

PDIs are protein chaperones and are central to maintaining cancer cell metabolism. Additionally, PDI inhibitors can cause cancer cell death through the accumulation of impaired proteins and dysregulated cellular stress responses. A combination of these effects is known as proteotoxicity, a unique and promising therapeutic strategy that may be especially effective in targeting cancers that are resistant to therapy.

In the US, nearly 612,000 people6are projected to die from cancer in 2024 and, resistance to anticancer drugs will be implicated in 90% of those deaths7. To date, no PDI inhibitor has reached the clinic due to the complexities related to selecting and mapping the molecules that will most accurately target the right PDI enzymes. There are more than 20 PDI enzymes, with each playing a slightly different and often biologically redundant role.  

Oregon Therapeutic’s lead drug-candidate XCE853 is known to target PDIs of specific interest for cancer. Lantern Pharma and Oregon Therapeutics believe that computational tools, including foundational models, machine learning and large-scale molecular analysis can offer an ideal and streamlined pathway for breaking through these data and decision complexities. 

Oregon Therapeutics has previously performed preclinical studies indicating that in addition to ovarian and pancreatic cancer, XCE853 may also be particularly active in renal, prostate, lung, breast, and head and neck cancers, and leukaemia based on preclinical cell-line studies. 

Official comments 

“To date, our first-in-class metabolic inhibitor, XCE853, has exhibited robust preclinical efficacy in both in vitro and in vivo models across multiple cancer types,” said Marc-Henry PITTY, CEO of Oregon Therapeutics. “Lantern’s RADR AI platform will leverage the in vitro and in vivo data to potentially advance XCE853 development in a highly targeted manner and will help inform disease indications and biomarker signatures that can aid in the design of future clinical trials and in the pursuit of combination therapies with other approved cancer drugs. Our team is looking forward to efficiently selecting among the landscape of ideal development options and efficiently de-risking future clinical development decisions.”  

Oregon project leader, Dr Sandrine Courtès, who has been developing the collaboration with Lantern Pharma, added: “PDIs Inhibitors have a great potential, since this molecular target is highly expressed in several cancer types, supports tumour growth and is associated with clinical outcomes.” 

Megan Thomas, Multimedia Editor, DDW

References 
  1. Prevost G.P. et al. Abstract 3760: XCE853 is a promising protein disulfide isomerase (PDI) inhibitor exhibiting a strong inhibitory activity in preclinical tumor models. Cancer Res. (2016) 76 (14_Supplement): 3760. https://doi.org/10.1158/1538-7445.AM2016-3760 
  2. Shili Xu, Saranya Sankar, Nouri Neamati, Protein disulfide isomerase: a promising target for cancer therapy, Drug Discovery Today, Volume 19, Issue 3, 2014, Pages 222-240, ISSN 1359-6446, https://doi.org/10.1016/j.drudis.2013.10.017. (https://www.sciencedirect.com/science/article/pii/S135964461300384X) 
  3. Powell LE, Foster PA. Protein disulphide isomerase inhibition as a potential cancer therapeutic strategy. Cancer Med. 2021 Apr;10(8):2812-2825. doi: 10.1002/cam4.3836. Epub 2021 Mar 20. PMID: 33742523; PMCID: PMC8026947. 
  4. Yu, Won et al. 2014, Korean J Intern Med 29(5): 580-587), brain tumors (Zou et al. 2018, Oncol Rep. Feb;39(2):501-510.) 
  5. Samanta et al. 2017, Oncotarget. Nov 28; 8(61): 103543–103556 
  6. Siegel R.L., Giaquinto A.N., and Jemal A. Cancer statistics 2024. CA: A Cancer Journal for Clinicians. (Jan/Feb 2024) 74 (1): 12-49. https://doi.org/10.3322/caac.21820 
  7. Longley D.B. and Johnston P.G. Molecular mechanisms of drug resistance. The Journal of Pathology. (Jan 2005) 205 (2): 275-292. https://doi.org/10.1002/path.1706 
  8. Rutkevich L.A., Cohen-Doyle M.F., Brockmeier U., Williams D.B. (2010). Molecular Biology of the Cell. 21:3093–105. https://doi.org/10.1091/mbc.e10-04-0356 
  9. Watanabe M.W., Laurindo, F.R.M, Fernandes, D.C. Frontiers in Chemistry. (2014). Methods of measuring protein disulfide isomerase activity: a critical overview. 2, 73. https://www.frontiersin.org/articles/10.3389/fchem.2014.00073/full 

Related Articles

Join FREE today and become a member
of Drug Discovery World

Membership includes:

  • Full access to the website including free and gated premium content in news, articles, business, regulatory, cancer research, intelligence and more.
  • Unlimited App access: current and archived digital issues of DDW magazine with search functionality, special in App only content and links to the latest industry news and information.
  • Weekly e-newsletter, a round-up of the most interesting and pertinent industry news and developments.
  • Whitepapers, eBooks and information from trusted third parties.
Join For Free