Targeted Therapy For Cancer Treatment Explained


What is Targeted Therapy for Cancer Treatment?

Targeted anticancer agents are drugs that produce their anticancer effect by selectively modifying a target key to the growth of cancer cells. 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. Targeted therapy helps in the selective destruction of cancer cells while sparing normal cells, which leads to a decrease in the side effects.

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.

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
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
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
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

EGFR=Epidermal growth factor receptor; HER2=Human epidermal growth factor receptor 2; CDK=Cyclin dependent kinase; ALL=Acute lymphoblastic leukemias; CLL=Chronic lymphoblastic leukemia; AML=Acute myelogenous leukemias; CML=Chronic myelogenous leukemia; NSCLC=Non-small cell lung cancer; PDGFR-α=Platelet-derived growth factor receptor; mTOR= Mammalian target of rapamycin; VEGF=Vascular endothelial growth factor; PARP=Poly (ADP-ribose) polymerase; SERD=Selective estrogen receptor degrader; SERM= selective estrogen receptor modulator; BCL-2=B-Cell Lymphoma-2; IDH2=Isocitrate dehydrogenase 2; CCR4=CC chemokine receptor 4; SLAMF7=Signaling Lymphocytic Activation Molecule Family member 7.

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. Sometimes, 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 druggable targets, an oncologist can select the best-suited treatment for the patient.

In some cases, especially when the disease is not responding to standard chemotherapy/radiotherapy, targeted therapy may be given to prolong the survival of cancer patients provided the presence of a targeted defect exists in cancer cells.

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.

Moreover, genetic mutations vary within patients as well, i.e. all cancer cells within a patient do not harbor the same set of mutations. This makes only selected cancer cells susceptible to a particular targeted drug. While cancer cells with a different set of mutations keep growing and eventually the disease becomes resistant to the targeted drug. This is why targeted drugs are generally combined with other targeted drugs, chemotherapeutic drugs, or radiotherapy for better efficacy.

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.

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. The most common side effect of targeted therapy is skin problems that usually develop slowly over days to weeks. 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.


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