Treatment specific to a target specific to a particular cancer.
Targeted therapy is one of the major modalities of medical treatment for cancer, while others being hormonal therapy and cytotoxic chemotherapy.
As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells.
Most agents for targeted therapy are biopharmaceuticals.
Biopharmaceuticals can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
Nanoengineered enzymes that bind to a tumor cell are another type of targeted therapy that the body’s natural cell degradation process can digest the cell, effectively eliminating it from the body.
Targeted cancer therapies are expected to be more effective than older forms of treatments and less harmful to normal cells.
Many targeted therapies are immunotherapy.
Immunomodulators are one type of biological response modifiers.
The most successful targeted therapies preferentially target a protein or enzyme that carries a mutation or other genetic alteration that is specific to cancer cells and not found in normal host tissue.
Imatinib is a successful molecular targeted therapeuticis imatinib, a tyrosine kinase inhibitor with exceptional affinity for the oncofusion protein BCR-Abl which is a strong driver of tumorigenesis in chronic myelogenous leukemia.
Molecular targeted therapeutics targeting mutated oncogenes, include PLX27892 which targets mutant B-raf in melanoma.
There are targeted therapies for lung cancer, colorectal cancer, head and neck cancer, breast cancer, multiple myeloma, lymphoma, prostate cancer, melanoma and other cancers.
Biomarkers are usually required to aid the selection of patients who will likely respond to a given targeted therapy.
Co-targeted therapy involves the use of one or more therapeutics aimed at multiple targets, for example PI3K and MEK, in an attempt to generate a synergistic response and prevent the development of drug resistance.
The main categories of targeted therapy are currently small molecules and monoclonal antibodies.
Many are tyrosine-kinase inhibitors.
Bortezomib (Velcade) is an apoptosis-inducing proteasome inhibitor drug that causes cancer cells to undergo cell death by interfering with proteins.
The selective estrogen receptor modulator tamoxifen has been described as the foundation of targeted therapy.
Janus kinase inhibitors
Apatinib is a selective VEGF Receptor 2 inhibitor.
Hedgehog pathway inhibitors
Small molecule drug conjugates
A small molecule drug conjugate consisting of a small molecule targeting the folate receptor for platinum-resistant ovarian cancer.
Serine/threonine kinase inhibitors (small molecules)
Pembrolizumab (Keytruda) binds to PD-1 proteins found on T cells. Pembrolizumab blocks PD-1 and help the immune system kill cancer cells.
It is used to treat melanoma, Hodgkin’s lymphoma, non-small cell lung carcinoma and several other types of cancer.
Rituximab targets CD20 found on B cells.
It is used in non Hodgkin lymphoma
Trastuzumab targets the Her2/neu (also known as ErbB2) receptor expressed in some types of breast cancer
Cetuximab target the epidermal growth factor receptor (EGFR).
It is approved for use in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck.
Panitumumab also targets the EGFR. It is approved for the use in the treatment of metastatic colorectal cancer.
Bevacizumab targets circulating VEGF ligand.
It is approved for use in the treatment of colon cancer, breast cancer, non-small cell lung cancer, and is investigational in the treatment of sarcoma.
Many antibody-drug conjugates (ADCs) are being developed.
Therapies with drugs and Biologics designed to affect cancer cell growth by blocking or interfering with specific molecular pathways in the cancer cell.
The target could be responsible for the pathophysiology of a cancer-BCR/ABL oncoprotein in CML.
Targeted therapy inhibits proteins that are abnormally activated as a result of somatic genetic alterations.
Use of targeted therapy usually requires verification through molecular testing that the patient’s tumor harbors the molecular biomarkers that is the target of the drug or biologic product.
Targeted agents are more specific to cancer cells than are cytotoxic agents that target cell replication.
The target may be expressed on a cancer cell, which may or may not be a contributing factor to the pathogenesis of the cancer-CD20 on B cell lymphoma or CD33 in AML.
Responses with the use of targeted agents are characterized by change in appearance of lesions without necessarily size changes, this defies the traditional RECIST-based assessment of progression.
Criteria used to define disease response is not clear cut in targeted therapy and the pattern of progression is different when comparing nontargeted and traditional chemotherapy.
No cosensus on how to adequately define criteria for drug resistance to targeted therapy.
Biologic agents have been associated with cardiotoxicity, hemorrhage, or visceral perforation, thromboembolic disease, anemia, diarrhea, hypothyroidism, and skin rash.
Majority of targeted agents are used in a continuous fashion making cumulative toxicity common.
EGFR inhibitors frequently associated with a papulopustular rash.
All EGFR inhibitors are associated with a papulopustular rash, the most common dermatologic adverse effect of this drug class, and seen in 90% of patients (Perez-Zoler R).
Hypertension associated with inhibitors of the vascular endothelial growth factor receptor (VEGFR) signaling pathway.
Multikinase inhibitors sorafenib and sunitinib are associated with a papulopustular rash that is less frequent and milder than the rash associated with EGFR inhibitors.