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-

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.