Name: how targeted cancer drugs work
Uploaded: 2021-04-07T12:12:03.000Z
Duration: 2 min 57 s
Channel: JoVE

K12 Standards

Arizona Science Standards

High School

Life Science

HS.L1

HS.L1U3.23

Targeted Cancer Therapies

Traditional cancer therapies, such as chemotherapy and radiotherapy, are not highly selective in targeting cancer cells and, therefore, have various side effects on normal cells of the body as well.&#160;
In contrast, targeted cancer therapies use drugs designed to target specific molecular structures that are present only in the cancer cells, and are absent in normal cells.
For example, healthy cells have two separate genes, BCR and ABL1. In chronic myeloid leukemia, chromosomal translocation fuses a part of the BCR gene with the ABL1 gene, leading to the synthesis of fusion protein BCR/ABL1.
This abnormal fusion protein drives uncontrolled cell proliferation and results in an excessive number of white blood cells in the bloodstream.
Imatinib mesylate is a small molecule kinase inhibitor that can specifically target the BCR/ABL1 fusion protein, preventing its activity and the downstream signaling pathways that control cell proliferation.
The drug also inhibits the ABL1 protein in the healthy cells, but additional redundant tyrosine kinases in such cells cover up for the loss of function of the ABL protein.
Imatinib mesylate is an example of a successful targeted molecular therapy again

targeted cancer therapies

The targeted cancer therapies, also known as &#8220;molecular targeted therapies,&#8221; take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific molecular targets to treat different kinds of cancers.
<h4>Angiogenesis inhibitors </h4>
Angiogenesis plays a huge role in the tumor microenvironment by providing necessary oxygen and nutrients to the growing tumor cells. Therefore, the use of specific inhibitors, such as bevacizumab that can bind circulating vascular endothelial growth factors and block the formation of new blood vessels, can help to restrict the growth of tumor cells.
<h4>Monoclonal antibodies</h4>
Another commonly used strategy against cancer is the use of monoclonal antibodies, such as alemtuzumab, trastuzumab, and cetuximab, that can directly target tumor cells. While some of these antibodies target a specific marker on the cancer cells, others just improve the immune response in the body.
<h4>Proteasome inhibitors</h4>
The ubiquitin-proteasome pathway plays a crucial role in apoptosis, cell survival, cell-cycle progression, DNA repair, and antigen presentation in eukaryotic cells. Inhibitors of this pathway, such as bortezomib, carfilzomib, and ixazomib, are successfully used to treat myeloma and mantle-cell lymphoma (MCL).
<h4>Signal transduction inhibitors</h4>
Most cancer cells have abnormal signal transduction pathways that lead to their uncontrolled cell growth, proliferation, and survival. The development of drugs that can inhibit the aberrant signal transduction elements in the cancer cells, such as the surface receptors or the downstream effectors, such as kinases, is a promising avenue for targeted therapy. For example, epidermal growth factor receptor or EGFR is a transmembrane receptor tyrosine kinase that is abnormally expressed in some cases of cancer. Gefitinib, an FDA-approved drug, is an EGFR inhibitor that is successfully used for the treatment of non-small cell lung cancer.

The targeted cancer therapies, also known as &#8220;molecular targeted therapies,&#8221; take advantage of the molecular and genetic differences between ...

Education

JoVE Core

Molecular Biology

Unit 2

Cancer

KEY TERMS AND CONCEPTS

how targeted cancer drugs work

Targeted cancer drugs are designed to act on specific molecular features that help cancer cells grow and spread. They are also called molecular targeted therapies. These treatments depend on a detailed understanding of the differences between cancer cells and normal cells, so the drug can focus on the cancer cell’s driving signals without harming healthy cells as much.

One major group is angiogenesis inhibitors. Angiogenesis means the formation of new blood vessels, which tumors use to get oxygen and nutrients. Bevacizumab is one example. It binds circulating vascular endothelial growth factors and blocks new blood vessel formation, which can slow tumor growth.

Another group is monoclonal antibodies. These are lab-made antibodies that can directly target tumor cells. Some, such as alemtuzumab, trastuzumab, and cetuximab, bind to a specific marker on cancer cells. Others help strengthen the body’s immune response against the tumor.

Proteasome inhibitors are also used in cancer treatment. The ubiquitin-proteasome pathway helps control apoptosis, cell survival, cell-cycle progression, DNA repair, and antigen presentation in eukaryotic cells. Drugs such as bortezomib, carfilzomib, and ixazomib block this pathway and are used to treat myeloma and mantle-cell lymphoma (MCL).

A final group is signal transduction inhibitors. Signal transduction is the cell’s communication system, and many cancer cells have abnormal pathways that drive uncontrolled growth, proliferation, and survival. These drugs can block surface receptors or downstream effectors such as kinases. EGFR, or epidermal growth factor receptor, is one example of a receptor that can be abnormally expressed in some cancers. Gefitinib is an FDA-approved EGFR inhibitor used to treat non-small cell lung cancer.

How Targeted Cancer Drugs Work

what is cancer?

Cancer Cells and How They Spread

Cancer cells and how they spread are explained through the normal behavior of cells and tissues. In a healthy body, cells must coordinate carefully. They rest, grow, divide, differentiate, or die in ways that support the organism. Cancer begins when this control breaks down. Cells divide without stopping and invade nearby tissues or organs. Cancer cells show two heritable traits. They reproduce against normal limits on cell growth and division, and they invade and colonize other cells and...

cancers originate from somatic mutations in a single cell

cancers-originate-from-somatic-mutations-in-a-single-cell

How Mutations Drive Cancer Growth

Cancer develops when mutations change the genes that control the cell cycle and let healthy cells keep dividing. A cancer can begin from a single mutation in one starting cell. As that cell line keeps growing, it can collect more mutations and eventually become malignant. One example is chronic myelogenous leukemia, or CML. It often begins as a non-lethal rise in white blood cells and then grows worse over several years before becoming life-threatening. This shows how cancer can progress step...

tumor progression

From Polyp to Metastatic Cancer

Tumor progression is the stepwise change that can turn an early tumor into a more aggressive and malignant cancer. Foulds first described this pattern in the 1950s. Colon cancer is one of the best-known examples, because researchers can follow its changes over time. In colon cells, an early mutation in the APC gene can create a small growth on the colon wall called a polyp. Over time, this polyp may grow into a benign, pre-cancerous tumor. Later mutations in the K-ras and p53 genes can push...

adaptive mechanisms in cancer cells

How Cancer Cells Survive and Spread

Cancer cells survive and spread by gaining genetic changes that help them grow faster than normal cells. These changes build up quickly because defects in DNA repair let mutations appear at an unusually high rate. From an evolutionary point of view, this genetic instability gives cancer cells an advantage as they develop. As mutant cell lines keep changing, they collect helpful mutations that support cancer progression. These cells can divide without fully differentiating, form large cell...

the tumor microenvironment

How Tumors Remodel Their Surroundings

Tumors remodel the local tissue environment to support cancer growth. This surrounding area is called the stroma. It includes several cell types, a basal membrane, and blood vessels. As normal cells mutate and become cancer cells, the nearby environment changes with them. The tumor microenvironment, or TME, is made of the developing tumor and the stromal cells around it. Communication between cancer cells and these surrounding cells is important because it disrupts normal tissue balance and...

metastasis

How Cancer Cells Spread to New Sites

Metastasis is the spread of cancer cells from one part of the body to another. Cancer cells can move through blood vessels, called hematogenous spread, or through lymph vessels. This process helps form tumors in distant tissues. A key step in metastasis is epithelial-to-mesenchymal transition, or EMT. EMT is a normal developmental process seen in wound healing and embryogenesis, but it also appears in cancer metastasis. It is triggered by transforming growth factor-beta (TGF-β) or receptor...

cancer-critical genes i: proto-oncogenes

Oncogenes and Cell Growth Control

Genes usually make proteins that help healthy cells work properly. When mutations change how these genes are expressed, the cell’s traits can change too. If critical genes that control the cell cycle and growth signals are disrupted, cell cycle progress can go off track and cells may divide without control. Over time, these cells can form tumors. Cancer-critical genes are the genes that drive this process. They fall into two main groups: proto-oncogenes and tumor suppressor genes.

mechanisms of retrovirus-induced cancers

How Retroviruses Trigger Cancer

Retroviruses can trigger cancer by changing how host cells grow and divide. These RNA viruses have been shown to cause cancers in species such as chickens, mice, cats, and monkeys. After infection, the viral RNA genome is reverse-transcribed into DNA. It first becomes single-stranded DNA and then double-stranded DNA. This double-stranded form, called proviral DNA, integrates into the host genome. The host cell then transcribes the proviral DNA along with its own chromosomal DNA. This process...

the ras gene

Ras Proteins: Cellular Switches in Cancer

Ras proteins are small GTPase signaling proteins that help control cell proliferation, differentiation, and cell survival. In humans, the Ras gene family has three main members: HRas, NRas, and KRas. These genes produce four closely related proteins: HRas, NRas, KRas4A, and KRas4B. Ras proteins work like molecular switches. They cycle between an active GTP-bound form and an inactive GDP-bound form. Guanine nucleotide exchange factors, or GEFs, help exchange GDP for GTP and turn Ras on.

loss of tumor suppressor gene functions

Tumor Suppressor Genes and Cancer Risk

Tumor suppressor genes help protect cells from becoming cancerous. They can slow cell division, repair DNA mistakes, or trigger apoptosis, which is programmed cell death, when damage cannot be fixed. These jobs help stop damaged cells from multiplying. When a tumor suppressor gene mutates or is lost, cells may begin to grow out of control. A single working copy is usually enough for the cell to keep normal control of the cell cycle. Cancer develops when both copies are inactivated or lost. <br...

mtor signaling and cancer progression

How mTOR Drives Cell Growth in Cancer

mTOR signaling helps control cell growth by balancing building processes and breakdown processes. mTOR stands for mammalian target of rapamycin. It was discovered in 1994 because it binds directly to rapamycin. Its name also comes from a yeast protein called TOR. In mammalian cells, the mTOR protein complex responds to environmental cues such as nutrients and growth factors. It supports anabolic processes, which are the cell’s building steps. These include the synthesis of proteins, lipids,...

cancer stem cells and tumor maintenance

How Cancer Stem Cells Drive Relapse

Cancer stem cells help tumors survive treatment and return after therapy. These residual cells can remain after early diagnosis and treatment, and they often lead to tumor recurrence. They are important because they can self-renew and also produce more than one cell type, which makes them hard to eliminate. Cancer stem cells are thought to come from normal stem cells or progenitor cells in a tissue. Normal stem cells usually stay quiet, or quiescent, until a signal tells them to divide or...

mouse models of cancer study

Mouse Cancer Models in Drug Testing

Mouse cancer models help scientists study how tumors start, grow, and respond to treatment. Mice are widely used because they are similar to humans in many biological and body functions. They are also easy to keep and breed in the laboratory, so many inbred strains are available for research. Cancer research has made major use of genetically modified mice. Transgenic mice carry an added gene, while knockout and knock-in mice have genes deleted or changed with genetic engineering. If a gene...

cancer prevention

Diet and Exercise in Cancer Risk

Diet and exercise can play a major role in cancer risk. Studies show that about 50% of cancer cases may be prevented through a healthy lifestyle, regular exercise, and a modest cancer prevention diet. Populations that eat more fruits and vegetables tend to have lower cancer rates. In contrast, diets high in animal fat, red meat, junk food, or calories are linked with a higher risk of cancer. Plant compounds called phytochemicals may also help protect against cancer. These natural chemicals...

cancer therapies

Combining Cancer Treatments

Cancer treatments often combine surgery, radiation therapy, and chemotherapy. These methods are used to treat cancer patients, but they can also damage normal cells. Cancer cells can also change quickly and become resistant to chemical agents or radiation therapy. Not every cancer responds to the same therapy. Some cancer cells respond to one treatment, while others respond to another because they carry different mutations. The best treatment depends on the type of cancer and how far it has...

Targeted cancer drugs are designed to act on specific molecular features that help cancer cells grow and spread. They are also called molecular targeted therapies. These treatments depend on a detailed understanding of the differences between cancer cells and normal cells, so the drug can focus on the cancer cell’s driving signals without harming healthy cells as much. One major group is angiogenesis inhibitors. Angiogenesis means the formation of new blood vessels, which tumors use to get...

treatment resistant cancers

How Cancer Cells Resist Treatment

Cancer cells can resist treatment by changing how they respond to anticancer drugs. This resistance makes cancer harder to treat. It also helps explain why cancer remains a major health problem. Cancer is the second leading cause of death in the United States. Cancer cells are genetically unstable, so they can mutate quickly. They can also change their microenvironment, which helps them avoid immune surveillance. In many tumors, resistance develops when cells alter drug transport or drug...

combination therapies and personalized medicine

combination-therapies-and-personalized-medicine

Cancer Treatment Pairings and DNA-Guided Care

Combination therapy for cancer uses two or more treatments together to improve patient outcomes. This approach can extend life span and help protect vital organs and tissue from the damage that may come from using one treatment too much. It also attacks more than one cancer-causing pathway, which can lower the chance of treatment resistance. A clear example is the pair of acetazolamide and sulforaphane. Large tumors often have a low-oxygen, acidic center, and cancer cells respond by making...

cancer-critical genes ii: tumor suppressor genes

cancer-critical-genes-ii-tumor-suppressor-genes

How Tumor Suppressor Genes Prevent Cancer

Tumor suppressor genes help keep cell growth under control. They can slow cell division, repair DNA errors, or trigger apoptosis, which is programmed cell death. These jobs protect healthy cells and help maintain normal cell cycle progression. When a tumor suppressor gene is disrupted, cells can lose this control. Loss-of-function mutations in these genes can let damaged cells keep dividing. Over time, that unchecked growth can contribute to tumor formation and cancer. Most tumor suppressor...

the retinoblastoma gene

Retinoblastoma Gene and Childhood Eye Tumors

The retinoblastoma gene, or Rb, is a tumor suppressor gene linked to a rare eye cancer in children. Tumor suppressor genes are normal genes that help slow cell division, fix DNA mistakes, or trigger apoptosis, which is programmed cell death when damage cannot be repaired. These genes help protect the body from damaged cells growing out of control. Rb was the first tumor suppressor gene ever identified. It was discovered through study of retinoblastoma, one of the most common malignant tumors...

rous sarcoma virus (rsv) and cancer

How RSV Uses Src to Drive Tumor Growth

Rous sarcoma virus, or RSV, is a retrovirus that can trigger tumor growth in chickens. F. Peyton Rous first discovered it in 1911 as a filterable transmissible agent. His work showed that some cancers can be caused by infectious agents. He later received the Nobel Prize in 1966 for this discovery, which also helped lead to the finding of other cancer-causing viruses in animals and humans. RSV carries two copies of a plus-strand RNA genome. Its genome has four main open reading frames, or ORFs:...

key terms and concepts

Learn how targeted cancer drugs attack tumor-specific signals, from angiogenesis inhibitors and monoclonal antibodies to proteasome and EGFR inhibitors.

How Targeted Cancer Drugs Work | JoVE K12

molecular biology

JoVE Core Molecular Biology showcases the molecular processes of the cell through clear and concise animated video lessons. Additionally, in scientist-in-action videos, these concepts' application is demonstrated through real experiments in modern laboratories.

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Structural Organization of the Human Body: An Overview

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Negative and Positive Feedback

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HS.L1U1.20

What is the Cell Cycle?

The cell cycle refers to the sequence of events occurring throughout a typical cell&#8217;s life. In eukaryotic cells, the somatic cell cycle has two ...

Interphase

The cell cycle occurs over approximately 24 hours (in a typical human cell) and in two distinct stages: interphase, which includes three phases of the ...

The Cell Cycle Control System

Positive Regulator Molecules

Inhibition of CDK Activity

S-Cdk Initiates DNA Replication

M-Cdk Drives Transition Into Mitosis

Mitogens and the Cell Cycle

Replicative Cell Senescence

Abnormal Proliferation

cells-coordinate-growth-and-proliferation

Cells Coordinate Growth and Proliferation

Construct an explanation for how cellular division (mitosis) is the process by which organisms grow and maintain complex, interconnected systems.

HS.L1U1.22

What is Cancer?

Cells and tissues must meticulously coordinate their activities&#160;for the normal functioning of the human body. Therefore, they exhibit socially ...

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate ...

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are ...

Cancer Prevention

Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular ...

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, ...

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify ...

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a ...

Obtain, evaluate, and communicate the ethical, social, economic and/or political implications of the detection and treatment of abnormal cell function.

How Targeted Cancer Drugs Work

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