What is Targeted Therapy for Cancer Treatment?
Cancer is a heterogeneous disease, that is, all individuals with the same cancer type do not contain the same mutations/alterations. Thus, the targeted therapy is designed to target a specific alteration/mutation.Targeted anticancer agents are drugs that produce their anticancer effect by selectively modifying a target key to the growth of cancer cells. Targeted therapy helps in the selective destruction of cancer cells while sparing normal cells, which leads to a decrease in the side effects. Examples of such targets include genetic or epigenetic alterations, chromosome rearrangements, cell-surface proteins/antigens, or certain molecular pathways in the cancer cells that regulate tumor growth, progression, and survival.
What types of targeted therapies are available today?
A classic example of a targeted anticancer drug is imatinib, a selective tyrosine kinase inhibitor (TKI) that has revolutionized the treatment strategy for chronic myeloid leukemia (CML). Since then many targeted drugs have been developed and come into practice. The following table list various types of targeted cancer therapy available today-
| Targeted Therapy Category/ Mechanism of action | Drug | Indication |
| EGFR inhibitors | Cetuximab | Colon, rectal, head & neck cancer, non-small lung cancer, and non-melanoma skin cancer |
| Panitumumab | Colon, penile, and rectal cancer | |
| HER2 inhibitors | Trastuzumab | Breast, gastric, and esophageal cancer |
| Pertuzumab | Breast cancer | |
| Ado-trastuzumab emtansine | Breast cancer | |
| Kinase inhibitors | Axitinib | Kidney cancer |
| Bosutinib | ALL and CML | |
| Cabozantinib | Thyroid cancer | |
| Crizotinib | NSCLC and sarcoma | |
| Dabrafenib | Melanoma with abnormal BRAF gene | |
| Dasatinib | ALL, CLL, CML, and soft tissue sarcoma | |
| Erlotinib | Bone, esophageal, kidney, pancreatic and NSCLC | |
| Ibrutinib | Leukemias and lymphomas | |
| Imatinib | Bone cancer, non-melanoma skin cancer, ALL, CML, melanoma, non-Hodgkin’s lymphoma, and soft tissue sarcoma | |
| Lapatinib | Bone, breast, and central nervous system cancers | |
| Nilotinib | ALL, CML, and soft tissue sarcomas | |
| Pazopanib | Kidney, thyroid, uterine cancer, and soft tissue sarcoma | |
| Ponatinib | ALL and CML | |
| Regorafenib | Colorectal cancer and soft tissue sarcoma | |
| Sorafenib | Bone, hepatobiliary, kidney, thyroid cancer, and sarcomas | |
| Sunitinib | Bone, kidney, neuroendocrine, thyroid cancer, and sarcoma | |
| Trametinib | Melanoma with abnormal BRAF gene | |
| Vandetanib | Thyroid cancer | |
| Vemurafenib | Melanoma with abnormal BRAF gene | |
| Lenvatinib | Kidney, liver, and thyroid cancer | |
| Idelalisib | CLL, non-Hodgkin lymphoma | |
| Copanlisib | Follicular lymphoma | |
| Acalabrutinib | Mantle Cell Lymphoma (MCL) | |
| Ruxolitinib | Myelodysplastic/myeloproliferative disorders | |
| Midostaurin | AML, aggressive systemic mastocytosis, mast cell leukemia | |
| Cobimetinib | Metastatic melanoma with a BRAF V600E or V600K mutation | |
| Encorafenib + Binimetinib | Metastatic melanoma with a BRAF V600E or V600K mutation | |
| Olaratumab (monoclonal antibody against PDGFR-α) | Metastatic soft tissue sarcoma | |
| PARP Inhibitors | Olaparib | Breast, ovarian, fallopian tube, primary peritoneal cancer |
| rucaparib | ||
| niraparib | ||
| mTOR inhibitors | Sirolimus | Bone cancers and soft tissue sarcoma |
| Everolimus | Breast, kidney, neuroendocrine cancers, soft tissue sarcomas, and Waldenström’s Macroglobulinemia | |
| Temsirolimus | Kidney and uterine cancer | |
| Hedgehog pathway inhibitor | Vismodegib | Non-melanoma skin cancer |
| Sonidegib | ||
| Immune system targets | Alemtuzumab (anti-CD52 antibody) | Non-Hodgkin lymphomas and Waldenström’s Macroglobulinemia |
| Brentuximab vedotin (target CD30) | T-cell lymphomas and Hodgkin lymphoma | |
| Ipilimumab (CTLA-4-blocking antibody) | Melanoma | |
| Ibritumomab tiuxetan (targets CD20) | Non-Hodgkin lymphoma | |
| Obinutuzumab (anti-CD20 antibody) | Non-Hodgkin lymphoma | |
| Ofatumumab (anti-CD20 antibody) | non-Hodgkin lymphoma and Waldenström’s Macroglobulinemia | |
| Rituximab (anti-CD20 antibody) | ALL, CNS cancers, Hodgkin lymphoma, non-Hodgkin lymphoma and Waldenström’s Macroglobulinemia | |
| Blinatumomab (bispecific CD19-directed CD3 T-cell engager) | ALL | |
| Daratumumab (anti-CD38 antibody) | Multiple myeloma | |
| VEGF receptor inhibitors | Bevacizumab | Breast, CNS, cervical, colon, kidney, ovarian, rectal, uterine cancer, sarcoma and NSCLC |
| Ziv-aflibercept | Colorectal cancer | |
| Ramucirumab | Stomach or gastroesophageal junction cancer | |
| CDK4 and CDK6 inhibitors | Palbociclib | Breast cancer |
| ribociclib | ||
| abemaciclib | ||
| Estrogen Targeted Drugs | Anastrozole (aromatase inhibitor) | Breast, ovarian, and uterine cancer |
| Exemestane (aromatase inhibitor) | Breast and uterine cancer | |
| Fulvestrant (SERD) | Breast cancer | |
| Letrozole (aromatase inhibitor) | Breast, ovarian, and uterine cancer | |
| Raloxifene (SERM) | Breast cancer | |
| Tamoxifen citrate (SERM) | Breast, ovarian, uterine cancer, and soft tissue sarcoma | |
| Toremifene citrate (SERM) | Breast cancer and soft tissue sarcoma | |
| Androgen targeted Drugs | Abiraterone acetate (androgen biosynthesis inhibitor) | Prostate cancer |
| Bicalutamide (nonsteroidal antiandrogen) | ||
| Enzalutamide (nonsteroidal antiandrogen) | ||
| Flutamide (nonsteroidal antiandrogen) | ||
| Nilutamide (nonsteroidal antiandrogen) | ||
| Apalutamide (nonsteroidal antiandrogen) | ||
| Proteasome targeted drugs | Bortezomib | Multiple myeloma, non-Hodgkin lymphoma, and Waldenström’s Macroglobulinemia |
| Carfilzomib | Multiple myeloma | |
| Ixazomib | Multiple myeloma | |
| Histone deacetylase targeted Drugs | Romidepsin | Non-Hodgkin lymphoma |
| Vorinostat | Multiple myeloma and a rare form of non-Hodgkin lymphoma | |
| Belinostat | Peripheral T-cell lymphoma | |
| Panobinostat | Multiple myeloma | |
| Folate-targeted Drugs | Pralatrexate | Non-Hodgkin lymphoma |
| Retinoic acid receptor targeted Drugs | Isotretinoin | Non-Hodgkin lymphomas and non-melanoma skin cancers |
| Tretinoin | Non-Hodgkin lymphoma | |
| Acitretin | Non-Hodgkin lymphoma and non-melanoma skin cancers | |
| Bexarotene | Non-Hodgkin lymphoma | |
| Alitretinoin | Kaposi’s sarcoma | |
| Nanoparticular Drugs | PEGylated liposomes encapsulating doxorubicin | Multiple cancer types |
| Nano albumin-bound paclitaxel (nab-paclitaxel) | ||
| Small-molecule inhibitor of BCL-2 | Venetoclax | CLL |
| IDH2 inhibitor | Enasidenib | AML |
| Miscellaneous | Inotuzumab ozogamicin (B-cell CD22 directed monoclonal antibody covalently attached to a cytotoxic agent) | ALL |
| Denileukin diftitox (interleukin-2 receptor directed recombinant diphtheria toxin) | Cutaneous T-cell lymphoma | |
| Mogamulizumab (CCR4 inhibitor) | Mycosis Fungoides (MF) and Sézary Syndrome (SS) | |
| Elotuzumab (SLAMF7 inhibitor) | Multiple myeloma |
How do I know if targeted therapy is right for me?
Patients who harbor a specific genetic/molecular alteration are generally considered as the suitable candidate for targeted cancer therapy. Also, the selection of targeted cancer therapy depends on the type of cancer a patient has. For assessing the most suitable candidates for targeted cancer therapy, molecular testing is done. Molecular testing helps in the detection of various genetic or epigenetic alterations, expression of certain defective proteins, or other defects in the cancer cells at the molecular level for which a targeted drug is available. Thus, based on the detection of such targets, an oncologist can select the best-suited treatment for the patient.
What are the advantages of Targeted therapy?
Targeted drugs are considered to be relatively safer than standard chemotherapeutic drugs as they are directed towards the specific molecular targets associated with the cancer cells. Thus, normal cells are spared by these drugs leading to a lower number (or less intensity) of side effects compared to those caused by standard chemotherapeutic agents. Targeted therapy has brought us to the era of personalized medicine. Since targeted therapy target specific genetic alterations, we have come very close to the era of personalized medicine for cancer.
What are the limitations of Targeted Therapy?
Cancer is a heterogeneous genetic disease, that is, all the patients with a similar cancer type do not harbor the same set of mutations. This renders the targeted drug to be useful only in some patient who harbor alterations targeted by the particular drug. All the genetic mutations/alterations identified by molecular/genetic testing cannot be targeted by the targeted drugs. This is why every patient cannot be benefitted by targeted therapy.
What are the side effects with Targeted Therapy?
Although targeted drugs are relatively safer than standard chemotherapeutic drugs, they can be associated with certain side effects depending upon the drug used and patient characteristics. Skin problems are commonly observed with EGFR inhibitors. Angiogenesis inhibitors are generally associated with side effects like high blood pressure, problem of bruising and bleeding, blood clots in the lungs and legs, heart attack, stroke, and delayed wound healing. Immune checkpoint inhibitors can sometimes cause serious immune reactions in the lungs, hormone-making glands, intestines, skin, liver, eyes, nerves, or other organs.
Where can I take Targeted Therapy in Delhi?
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with years of experience of treating cancer patients with Targeted Therapy. He has been trained at premier institutes of country and has practiced in leading cancer hospitals in Delhi, and currently practicing at Manipal Hospital, Dwarka. He works in close collaboration with surgical and radiation oncologists, oncopathologists, nuclear medicine, and genetic counselors for comprehensive cancer care for the patients.
What is the Cost of Targeted Therapy in Delhi?
Cost is determined by type of targeted therapy, total number of cycles, dose of the drug, along with other factors. It may also vary from hospital to other.