Clear all

Targeted Tumor Therapy Remixed—An Update on the Use of Small-Molecule Drugs in Combination Therapies

1 Posts
1 Users
0 Reactions
Joined: 9 years ago
Posts: 1194
Topic starter  

Very good overview from: 

Targeted Tumor Therapy Remixed—An Update on the Use of Small-Molecule Drugs in Combination Therapies

Principle/Substance Group Molecular Target Cancer Type/Ongoing Trials (Selection)
1.  Signaling/Kinase inhibitors    
- RAF-MEK-MAPK pathway inhibitors BRAFV600mut, MEK MM (LOGIC-2), NSCLC, CRC
- PI3K pathway inhibitors PI3K, AKT, mTOR, GSK3 MM (LOGIC-2), advanced solid tumors
- Cell cycle kinase inhibitors Cyclin-dependent kinases (CDK4/6) MM (LOGIC-2), NSCLC, solid tumors
- Growth factor signaling inhibitors Oncogenic receptor kinases Advanced cancers (multikinase inhibitors)
  - MET kinase MM (LOGIC-2), RC, NSCLC, lymphoma
- JAK-STAT pathway inhibitors Janus kinases (JAKs) advanced solid tumors, NSCLC, lymphoma
- FAK inhibitors (FAKi) Focal adhesion kinase (FAK) CRC, NSCLC, combination ImT
2.  Apoptosis modulators    
- BH3 mimetics, BCL-2/XL-inhibitors Intrinsic cell death (NOXA, PUMA, BIM) ALL (Venetoclax), n/f 1 (pre-clinical)
- SMAC mimetics Inhibitor of apoptosis proteins (IAPs) advanced solid tumors, NSCLC
- BCL-2 antisense oligonucleotides Anti-apoptotic BCL-2 members HM, MM (Oblimersen, withdrawn)
- p53 reactivation Tumor suppressor p53, MDM2/4 Advanced cancers, lymphoma, AML
- Death receptor activation Death receptors (FAS, TRAIL/APO-2) MM (DS-8273a), NSCLC, CRC
- Autophagy inhibitors Autophagy pathways CRC, HCC, advanced solid tumors
3.  DNA damage response inhibitors    
- PI3K/PIKK (ATM/ATR) inhibitors ATM and ATR kinases Advanced solid tumors, lymphoma, CNS
- Checkpoint kinase inhibitors CHK1 kinase, WEE kinase tumors (phase 0–II), ChT/RT combinations
- PARP inhibitors poly(ADP-ribose) polymerase (PARP) OC, combination therapies
4.  Epigenetic drugs    
- 5-Aza-(2-deoxy-)cytidine DNA-methyl-transferases (DNMT1-3) HM (MDS), MM
- HDAC inhibitors (HDACi) Histone deacetylases (HDAC1-10) HM, lymphoma, N/SCLC, MM
- EZH2 inhibitors Polycomb repressive complex (PRC) 2 Sarcoma, lymphoma, mesothelioma
- BET inhibitors BET family of histone readers Refractory HM (MDS, ALL), solid tumors
- DUB inhibitors (Histone) deubiquitinases n/f 1
- si/miRNAs microRNAs, lncRNAs, tumor mRNAs withdrawn, only biomarker studies
5.  Telomerase inhibitors    
- hTR antagonists/competitors hTR nucleotide (TERC) solid tumors, withdrawn (Imetelstat)
- hTERT inhibitors (Ti) Telomerase reverse transcriptase (TERT) withdrawn
6.  Redox drugs    
- Dimethylfumarate (DMF) BCL2, PARP1, NFκB-NRF2-KEAP1-axis Lymphoma (CTL), CNS (pre-clinical)
- Antioxidants (Vitamins, NAC, others) EMT, cytotoxicity reduction NSCLC, CRC, solid tumors, lymphoma
7.  Metabolic drugs    
- Metformin, Phenformin mTOR, TCA cycle MM, BC, OC, PC, advanced solid tumors
- PDK inhibitors (Dichloroacetate) Pyruvate dehydrogenase kinase, Glycolysis CNS tumors (completed), SCC
8.  Proteasome inhibitors    
Bortezomib, PS-341 (Ubiquitin)-Proteasome pathway Refractory solid tumors, HM
9.  Transdifferentiation inducers    
- Retinoids (ATRABexarotene) Nuclear RAR and RXR receptors HM, CNS, MM (pre-clinical)
- Unsaturated fatty acids PPARγ, adipogenic differentiation pathways CNS, MM (pre-clinical)
10.  Immunomodulators    
- T cell receptor signaling enhancers Ubiquitin ligases (CBL, ITCH, GRAIL, et al.) n/f 1
  Adaptor proteins, kinases  
- Kynurenine pathway inhibitors Indoleamine 2,3-dioxygenase (IDO1) MM (KEYNOTE-252/ECHO-301, halted)
11.  Others    
- Matrix metalloprotease inhibitors MMP, COL3 Advanced solid tumors (completed)
- WNT/β-Catenin inhibitors WNT ligand WNT-driven tumors (MM, CRC, others)