Treatment-refractory tumor models
Treatment-refractory solid tumors pose a significant challenge, as they have a poor prognosis and limited effective treatment options. Most well-known molecular mechanisms underlying treatment-resistance is epithelial-mesenchymal transition (EMT). To address this challenge, CMTX focuses on developing small molecule therapeutics specifically designed to target treatment-refractory cancer subtypes associated with EMT, such as gastric cancer with EMT subtype, colorectal cancer with CMS4 subtype, mesenchymal subtype of triple negative breast cancer, and glioblastoma tumor initiating cells etc.


The immune system plays crucial role in surveilling and eliminating tumor cells. However, tumor cells employ various strategies to evade immune attack, such as expressing immune checkpoint proteins like PD-L1 on their surface. PD-L1 binds to its immune checkpoint receptor PD-1, triggering an inhibitory signal in activated T cells and suppressing anti-tumor immunity. While monoclonal antibody therapies targeting PD-1/PD-L1 have shown clinical success, they have limitations, including low penetrance to solid tumors or the blood-brain barrier. The immunosuppressive tumor microenvironment (TME) contributes to immunotherapy resistance. Modifying the TME through multiple pathways can overcome checkpoint inhibitor resistance by reducing immunosuppressive cells, alleviating T-cell exhaustion, and/or facilitating T-cell infiltration into tumors. Small molecule drugs that modify the TME and enhance immune cell activity offer promise as breakthrough monotherapy or in combination with antibody-based immunotherapies.


  • Nicotinamide adenine dinucleotide (NAD+) is a vital coenzyme essential for oxidation/reduction reactions, DNA repair, and ATP generation. Failure in maintaining the NAD+ pool can lead to various diseases, including cancer, aging, and neurodegenerative disorders.
  • Axon degeneration is commonly observed in neurodegenerative diseases and serves as a prominent pathological feature in conditions like Alzheimer's disease (AD), Multiple sclerosis, Glaucoma, Traumatic brain injury, and peripheral neuropathies. NAD+ depletion caused by various genetic, chemical, and physical factors triggers axon degeneration.
  • Aberrant activation or dysfunction of the enzymes in the NAD+ biosynthesis pathways is directly or indirectly linked to the axon degeneration. NAMPT (nicotinamide phosphoribosyl transferase) and NMNAT2 (nicotinamide mononucleotide adenylyl transferase 2) in the salvage pathway catalyze the sequential synthesis of NMN and NAD+, respectively. SARM1 degrades NAD+ into nicotinamide and ADPR/cADPR by sensing the NMN/NAD+ ratio in the axon. Pharmacological modulation of NMN/NAD+ ratio by inhibiting or activating these enzymes can prevent the onset of axon degeneration and, consequently, halt the progression of neurodegenerative disorders.