Table 6.
Additional targeted therapies that have been clinically used for cancer treatment.
| Target | Generic name (Code name) | Brand name (Company) | First approved indication (Year) | Additional indication | Drug resistance mechanism (selected) | Side effects/toxicity (selected) | References |
|---|---|---|---|---|---|---|---|
| PARP |
Olaparib (AZD2281) |
Lynparza (AstraZeneca) |
Advanced ovarian cancer (2014) |
Maintenance treatment of ovarian cancer (2017, 2018, 2020) BRCA-mutated metastatic breast cancer (2018, 2022) Metastatic pancreatic cancer (2019, 2020) |
Restoration of homologous recombination repair and ADP-ribosylation (PARylation) reversion mutations |
Ileus, myelodysplastic syndrome, interstitial lung disease | 8,178,247 |
| PARP |
Rucaparib (AG014699) |
Rubraca (Clovis Oncology) |
Advanced ovarian cancer (2016) | Maintenance treatment of ovarian cancer (2018) |
Restoration of homologous recombination repair and ADP-ribosylation (PARylation) reversion mutations |
Nausea, vomiting, diarrhea, constipation, red blood cell count decrease, photosensitivity, renal impairment, dysgeusia | 8,178,247 |
| PARP |
Niraparib (MK-4827) |
Zejula (Tesaro) |
Recurrent ovarian cancer (2017) | Maintenance treatment for patients with platinum-responsive ovarian cancer regardless of biomarker status (2020) |
Restoration of homologous recombination repair and ADP-ribosylation (PARylation) reversion mutations |
Nausea, constipation, platelet/red blood cells count decrease, lymphangioleiomyomatosis | 8,178,247 |
| PARP |
Talazoparib (BMN-673) |
Talzenna (Pfizer) |
BRCA1/2-mutated advanced or metastatic HER2- breast cancer (2018) |
Restoration of homologous recombination repair and ADP-ribosylation (PARylation) reversion mutations |
Hematopoietic erythropenia, anemia, thrombocytopenia, pancytopenia, neutropenia | 8,178,247 | |
| DNMT1 |
Azacitidine (5-azacytidine) |
Vidaza (Pharmion Corporation) |
MDS2 (2004) | Adaptive responses of the pyrimidine metabolism network | Fatigue, constipation, mucositis, pneumonia, febrile neutropenia | 8,247,248 | |
| DNMT |
Decitabine (NSC 127716) |
Dacogen (Janssen-Cilag/Otsuka Pharmaceutical) Inqovi (oral tablet) (Otsuka Pharmaceutical) |
Dacogen : MDS (2006) |
Inqovi: MDS in combination with cedazuridine (2020) | Adaptive responses of the pyrimidine metabolism network | Fatigue, constipation, mucositis, pneumonia, febrile neutropenia | 8,247,249 |
| HDAC3 |
Vorinostat (SAHA) |
Zolinza (Merck) |
Relapse/refractory CTCL4 (2006) |
Overexpression of Bcl-2 family proteins JAK/STAT3 pathways HDAC alterations Epigenetic alterations Protection of oxidative stress Alterations in apoptosis/autophagy |
Diarrhea, fatigue, nausea, anorexia, dysgeusia, thrombocytopenia, pulmonary embolism, cardiac abnormalities | 250,251 | |
| HDAC |
Romidepsin (FK228, FR901228) |
Istodax (Celgene Corp./Bristol-Myers Squibb) |
CTCL (2009) | PTCL5 (2011) |
P-glycoprotein-mediated drug efflux HDAC alterations Epigenetic alterations Protection of oxidative stress Alterations in apoptosis/autophagy |
Thrombocytopenia, anemia, neutropenia, fatigue, nausea, vomiting, anorexia, tumor lysis syndrome | 250,251 |
| HDAC |
Belinostat (PXD-101) |
Beleodaq (Spectrum Pharmaceuticals) |
PTCL (2014) |
HDAC alterations Epigenetic alterations Alterations in apoptosis/autophagy |
Nausea, vomiting, tumor lysis syndrome, hepatic failure, cardiac abnormalities | 250,251 | |
| HDAC | Panobinostat (LBH-589) |
Farydak (Novartis/Secura Bio) |
MM7 (2015) |
HDAC alterations Epigenetic alterations Protection of oxidative stress Alterations in apoptosis/autophagy |
Severe diarrhea, nausea, vomiting, cardiac abnormalities | 250,251 | |
| EZH26 | Tazemetostat (E7438/EPZ6438) |
Tazverik (Epizyme) |
Relapsed/refractory follicular lymphoma (2020) | Metastatic or locally advanced epithelioid sarcoma (2020) | EZH2 Y726F, C663Y mutation | Nausea, asthenia, fatigue, alopecia, dry skin, diarrhea, neutropenia, thrombocytopenia | 252 |
| IDH18 |
Ivosidenib (AG-120) |
Tibsovo (Servier Pharmaceuticals) |
Relapse/refractory AML9 with an IDH1 mutation (2018) |
Frontline in AML patients with comorbidities (2019) IDH1-mutated cholangiocarcinoma (2021) |
Elevated 2-hydroxyglutarate Hypermethylation |
QT interval prolongation, IDH differentiation syndrome, anemia, thrombocytopenia | 8,91,216,253 |
| IDH2 |
Enasidenib (AG-221) |
Idhifa (Agios Pharmaceuticals) |
Relapse/refractory AML with an IDH2 mutation (2017) |
Elevated 2-hydroxyglutarate Hypermethylation |
Hyperbilirubinemia, thrombocytopenia, IDH differentiation syndrome |
216,253 | |
| Proteasome |
Bortezomib (PS-341) |
Velcade (Millennium/Takeda/Janssen Pharmaceutical) |
Relapse/refractory MM (2003) |
Proteasome mutation/overexpression Heat shock protein upregulation Autophagy Increased drug efflux Alterations in glutathione metabolism |
Peripheral neuropathy, hematologic toxicities, diarrhea, fatigue, dyspnea, zoster reactivation |
254,255 | |
| Proteasome |
Carfilzomib (PR-171) |
Kyprolis (Onyx Pharmaceuticals) |
Advanced MM (2012) |
Proteasome mutation Autophagy Increased drug efflux |
Hematologic toxicities, pneumonia, hyponatremia, fatigue, hypophosphatemia, infusion reactions, chest pain, heart failure |
254,255 | |
| Proteasome | Ixazomib (MLN2238) |
Ninlaro (Takeda) |
MM (2015) |
Proteasome mutation Autophagy |
Hematologic toxicities, fatigue, rash, decreased appetite, diarrhea, vomiting | 254,255 | |
| Bcl-2 |
Venetoclax (ABT-199) |
Venclexta (AbbVie/Genentech) |
CLL10 (2016) | AML (2018) |
BCL2 mutation Activation of the MAPK/Akt pathway Deregulation of energy metabolism Interaction with stromal cells |
Bone marrow suppression, nausea, vomiting, diarrhea | 8,256 |
| Smoothened | Vismodegib (GDC-0449) |
Erivedge (Genentech/Roche) |
BCC11 (2012) |
SMO mutations (e.g., D473H) SUFU/GLI2 copy number variation/mutation |
Muscle spasm, weight loss, alopecia, dysgeusia | 8,257 | |
| Smoothened |
Sonidegib (NVP-LDE225) |
Odomzo (Novartis) |
Locally advanced BCC (2015) |
SMO mutations SUFU/GLI2 copy number variation/mutation |
Nausea, dysgeusia, anorexia, muscle spasm, fatigue, creatine kinase elevation | 8,257 | |
| Smoothened |
Glasdegib (PF-04449913) |
Daurismo (Pfizer) |
AML (2018) |
SMO mutations SUFU/GLI2 copy number variation/mutation |
Thrombocytopenia, anorexia, peripheral edema, fatigue, neutropenia | 8,257 |
1DNMT: DNA methyltransferase.
2MDS: myelodysplastic syndrome.
3HDAC: histone deacetylase.
4CTCL: cutaneous T-cell lymphoma.
5PTCL: peripheral T-cell lymphoma.
6EZH2: enhancer of zeste homolog 2.
7MM: multiple myeloma.
8IDH: isocitrate dehydrogenase.
9AML: acute myeloid leukemia.
10CLL: chronic lymphocytic leukemia.
11BCC: basal cell carcinoma.
12ALCL: anaplastic large cell lymphoma.