Update: “2024-06-17”
This is the list of drugs that I have analyzed testing data of in DFCI.
Drug | Target/Mechanism | Clinical Applications | Development Stage | Company | Sources |
---|---|---|---|---|---|
DGKi | Inhibits diacylglycerol kinase, enhancing T-cell activation and immune responses by modulating DAG and PA signaling pathways. | Explored for potential application in enhancing the efficacy of cancer immunotherapies by boosting T-cell functionality. | Preclinical/early clinical trials | Bristol Myers Squibb | Nature Review on DGK inhibitors |
DS-1062a | TROP2-targeting antibody-drug conjugate with a cytotoxic topoisomerase I inhibitor payload (deruxtecan). | Targeted therapy for TROP2-expressing tumors, including non-small cell lung cancer and triple-negative breast cancer. | Phase II/III clinical trials | Daiichi Sankyo | Daiichi Sankyo’s Pipeline |
TAK-676 | Synthetic cyclic dinucleotide that acts as a STING agonist to activate the innate immune system. | Enhancing the effectiveness of existing cancer therapies by promoting immune cell infiltration and activation in tumors. | Phase I/II clinical trials | Takeda Pharmaceuticals | ClinicalTrials.gov Entry for TAK-676 |
ADU-S100 | Synthetic cyclic dinucleotide STING agonist that stimulates type I interferon and pro-inflammatory cytokine production. | Used in combination with immune checkpoint inhibitors to treat advanced solid tumors and cutaneous malignancies. | Phase I/II clinical trials | Aduro Biotech, Novartis | Aduro’s ADU-S100 Information |
DGKi:
- DGKi targets diacylglycerol kinase, an enzyme that regulates T-cell
activation by modulating the levels of diacylglycerol (DAG) and
phosphatidic acid (PA) within cells. Inhibition of this enzyme prevents
the conversion of DAG to PA, thereby maintaining DAG levels that are
crucial for downstream signaling events following T-cell receptor
engagement. This mechanism is believed to potentiate the immune response
by enhancing T-cell activation, proliferation, and survival, making it a
valuable target for boosting the effectiveness of T-cell-based cancer
immunotherapies.
DS-1062a:
- DS-1062a is designed to selectively target and kill TROP2-expressing
tumor cells. Its mechanism involves the targeted delivery of a potent
cytotoxic drug directly to the tumor cells, minimizing the impact on
non-targeted cells. This targeted approach allows for higher drug
concentrations at the tumor site, increasing tumor cell death while
reducing systemic toxicity. The ADC mechanism of DS-1062a utilizes the
internalization of the TROP2 antibody bound to its antigen on cancer
cells, followed by the intracellular release of the cytotoxic payload
that induces DNA damage and cell death.
TAK-676:
- TAK-676 utilizes the STING (Stimulator of Interferon Genes) pathway to
initiate and amplify the immune response against cancer cells. By
activating STING, TAK-676 triggers a cascade of signaling events that
lead to the production of type I interferons and other cytokines, which
enhance the body’s ability to detect and destroy cancer cells. This
activation is crucial for recruiting and activating immune cells,
including T cells and NK cells, into the tumor microenvironment, thereby
improving the overall effectiveness of cancer immunotherapies.
ADU-S100:
- ADU-S100 works by targeting the STING pathway, which plays a pivotal
role in the innate immune system’s ability to detect and respond to the
presence of tumor-derived or pathogen-derived cytosolic DNA. Activation
of this pathway by ADU-S100 leads to the induction of a strong
inflammatory response that promotes the activation and recruitment of
dendritic cells and T cells, key players in the adaptive immune
response. This mechanism enhances the visibility of tumors to the immune
system and facilitates the establishment of an effective anti-tumor
immune response, especially when used in combination with other
therapies that modulate the immune environment.
Mechanism of Action:
Clinical Applications:
Mechanism of Action:
Clinical Applications:
Advantages:
Disadvantages:
Advantages:
Disadvantages:
Advantages:
Disadvantages:
TROP2
Dxd
DS-1062a