Name: why some cancers resist treatment
Uploaded: 2023-04-30T18:28:52.000Z
Duration: 2 min 56 s
Channel: JoVE

Genetic instability allows cancer cells to acquire resistance to therapeutic drugs at a rapid rate.
For instance, while the initial drug treatment can eliminate most of the tumor cells, a small fraction of resistant mutant cells, called persisters, may tolerate the drug treatment and divide to form another tumor. All the cells of this new tumor are now resistant to the initial drug, resulting in therapeutic failure.
Cancer cells use several strategies to develop resistance to treatment.
The first is inhibition of drug activation. For example, the drug Cytosine arabinoside used to treat acute myelogenous leukemia must be activated intracellularly by multiple phosphorylation events. Cancer cells with mutations in this activation pathway can inhibit the activation of Cytosine arabinoside, leading to the drug resistance.&#160;
The second strategy is drug target modification. Consider the enzyme topoisomerase&#160; II, which reduces DNA supercoiling and enables smoother DNA replication in cells. Certain anticancer drugs target and inhibit the topoisomerase activity in order to stall DNA replication in rapidly dividing cancer cells.
However, resistant cancer cells can mutate the enzyme topoisomera

treatment resistent cancers

Treatment Resistent 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 their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or impaired apoptosis.
<h4>Origin of resistant cells</h4>
Given the heterogeneous nature of the cancer cells, a tumor can have various cancer cell subpopulations, each with distinct genetic fingerprints. Some of these cells may have pre-existing mutations or acquire new mutations that confer them drug resistance. Under therapeutic pressure, cancer cells obey the Darwinian law of evolution, and only the cells that are most adaptive and resistant to treatment survive and multiply to take over other susceptible cancer cell subpopulations.
<h4>Models for cancer resistance</h4>
Two models are put forward to explain resistance to anticancer drugs. One is the cancer stem cells (CSC) model, and another is the Environment-mediated drug resistance (EMDR) model.
Cancer stem cells or CSCs are quiescent cells with increased DNA repair efficiency, altered cell cycle parameters, or overexpression of anti-apoptotic properties or drug transporters. In this model, drug resistance is mostly caused by the intrinsic or acquired resistance of accumulating CSCs and not all cancer cells within a tumor.
In the Environment-mediated drug resistance (EMDR) model, cancer cells interact with the surrounding environment to enter a quiescent or dormant state to escape the drugs. Inside their protective zone composed of the tumor microenvironment, cancer cells undergo genetic changes until they acquire resistant phenotype. The cells can then relapse once the drug is withdrawn.

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 ...

Education

JoVE Core

Cell Biology

Unit 1

Cancer

KEY TERMS AND CONCEPTS

why some cancers resist treatment

Some cancers resist treatment and keep growing even after therapy. This video focuses on why that happens and how resistance changes cancer care.

Treatment resistance can develop when cancer cells survive drugs that should destroy them. The cells may avoid the drug’s effects, or they may keep dividing after treatment starts. This makes the cancer harder to control.

Understanding treatment-resistant cancer helps explain why some therapies work at first and then lose effect. It also shows why doctors may need to change treatment plans over time. The topic is important for studying how cancer cells adapt.

Why Some Cancers Resist Treatment

what is cancer?

How Cancer Cells Grow and Spread

Cancer is a disease in which cells grow and divide in an uncontrolled way. In healthy tissue, cell growth is regulated so the body can stay balanced and repair itself. In cancer, that control is lost. Cancer can start when cells in a specific tissue begin to divide too often. These abnormal cells may form a mass called a tumor. Some cancers stay in one place, while others spread to other parts of the body. The term cancer covers many diseases, not just one condition. Different cancers can...

cancers originate from somatic mutations in a single cell

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

Single-Cell Mutations Can Lead to Cancer

Cancer can begin when a somatic mutation appears in a single cell. A somatic mutation is a DNA change that is not inherited from a parent. It happens in a body cell during life and can give that cell a growth advantage. When the altered cell keeps dividing, its descendants carry the same mutation. Over time, this clone of cells can expand and form a tumor. This process helps explain how a cancer can start from one original cell rather than from the whole tissue at once. The idea also shows...

tumor progression

Tumor Growth and Spread

Tumor progression describes how a tumor changes over time. It includes tumor growth and, in some cases, spread to other parts of the body. These changes help explain why cancer can become more serious. As tumor cells divide, the tumor can increase in size. Some tumors stay in one place, while others become more aggressive. When a tumor spreads, cancer cells move away from the original site and start new tumors in other tissues. This process is linked to disease advancement and is a key part of...

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Cancer Cells Under Stress

Cancer cells survive by adjusting to stressful conditions in the body. They can change how they use energy, how they grow, and how they handle limited resources. These adaptive changes help the cells keep dividing even when their environment is harsh. One major example is hypoxia, which means low oxygen. Many tumors grow faster than their blood supply, so the cells must cope with oxygen shortage. Cancer cells can also use the Warburg effect, a way of making energy that relies heavily on...

the tumor microenvironment

Tumor Microenvironment: Cells Around Cancer

The tumor microenvironment includes the cells and materials that surround a tumor. It is an active part of cancer growth, not just a background setting. These nearby cells and signals can influence how a tumor develops and spreads. One important part of the tumor microenvironment is the extracellular matrix, or ECM. The ECM is the network of proteins and other materials outside cells that helps hold tissue together. Cancer cells can interact with this matrix as they grow and invade nearby...

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How Cancer Spreads: Metastasis

Metastasis is the spread of cancer cells from the original tumor to other parts of the body. It is a key step in cancer progression and helps explain why cancer can become more difficult to treat.

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Proto-oncogenes and Cell Growth Control

Proto-oncogenes are cancer-critical genes that help control normal cell growth. They play an important role in the signals that tell cells when to grow and divide. In healthy cells, these genes support regular cell behavior. Problems can begin when a proto-oncogene changes. A changed proto-oncogene may push a cell to divide too often or at the wrong time. This shift can contribute to cancer development. This topic focuses on proto-oncogenes as one class of cancer-related genes. It shows how...

cancer-critical genes ii: tumor suppressor genes

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

Tumor Suppressor Genes in Cancer

Tumor suppressor genes help keep cell growth under control and can limit cancer development. These genes act as safeguards by slowing the cell cycle, repairing damage, or triggering cell death when cells are too abnormal to continue dividing. When tumor suppressor genes are changed or lost, cells may divide when they should not. That loss of control can contribute to tumor growth. Understanding how these genes work helps explain why some cells become cancerous while others stay normal. The...

loss of tumor suppressor gene functions

Tumor Suppressor Gene Loss in Cancer

Tumor suppressor gene loss can help cancer cells grow and survive. Tumor suppressor genes normally help control cell growth and keep cells from dividing too quickly. When these gene functions are lost, that protection is reduced. This topic also includes how tumor suppressor genes can be turned off without changing the DNA code itself. Epigenetic changes are chemical changes that affect gene activity. They can silence a tumor suppressor gene and lower its function in the cell. Understanding...

the retinoblastoma gene

Retinoblastoma Gene and Cell Cycle Control

The retinoblastoma gene helps control the cell cycle. It is a tumor suppressor gene, which means it helps prevent cells from dividing when they should not. Its role is closely tied to normal cell growth and the checks that keep division under control. The gene is often discussed in relation to cancer because changes in its function can remove this control. When that happens, cells may keep dividing in an unregulated way. That loss of control can contribute to tumor formation.

mechanisms of retrovirus-induced cancers

How Retroviruses Lead to Cancer

Retroviruses can lead to cancer by changing how cells grow and divide. They are RNA viruses, and their genetic material is copied into DNA after infection. That DNA can then affect the host cell in ways that promote tumor formation. A key idea is the activation of proto-oncogenes. Proto-oncogenes are normal genes that help control cell growth, but they can become oncogenes, or cancer-causing genes, when their activity is altered. Retroviruses can contribute to this change and push infected...

rous sarcoma virus (rsv) and cancer

Rous Sarcoma Virus and the Src Gene

Rous sarcoma virus (RSV) is a cancer-causing virus linked to a specific gene called src. The virus is known for its role in helping scientists understand how some cancers develop at the molecular level. The src gene is a proto-oncogene, which means it is a normal gene with the potential to become cancer-related when altered. In RSV, this gene becomes the viral v-src version. That change is important because it connects a normal cellular gene to cancer-forming activity. RSV helped reveal that...

the ras gene

Ras Gene in Cell Signaling

The Ras gene helps control cell signaling. Ras proteins act as switches that pass signals inside a cell. These signals can affect growth and other cell responses. Ras is important in many cells because it helps move information from the cell surface to the cell interior. When this signaling system is working normally, the cell can respond in an organized way. Changes in Ras can disrupt that control.

mtor signaling and cancer progression

mTOR Pathway in Cancer Growth

mTOR signaling helps control cell growth, and changes in this pathway can support cancer progression. The mTOR protein is a key part of this signaling system. It helps cells respond to signals that tell them when to grow and divide. The transcript focuses on how mTOR signaling connects to cancer. When this pathway is altered, it can affect the behavior of cancer cells. Understanding this link helps explain why mTOR is an important topic in cancer biology. mTOR signaling is studied as part of...

cancer stem cells and tumor maintenance

Cancer Stem Cells in Tumor Growth

Cancer stem cells are a small group of cells inside a tumor that can support tumor growth and maintenance. They are studied because they may help explain why some cancers keep growing and return after treatment. Cancer stem cells can make new tumor cells. They also have the ability to self-renew, which means they can produce more cells like themselves. This makes them important in the long-term survival of the tumor. Some cancer stem cells may also resist therapy better than other tumor cells.

mouse models of cancer study

Mouse Models for Cancer Research

Mouse models for cancer research help scientists study how tumors form and grow in a living system. Mice are used because they can be matched to many human cancer features. They also allow researchers to test ideas before moving to clinical work. These models can include mice that naturally develop tumors and mice that are engineered to carry cancer-related changes. Some models are designed to mimic specific cancers, while others are used to study general tumor behavior. Together, they give...

cancer prevention

Lowering Cancer Risk

Cancer prevention focuses on lowering the chance that cancer will develop. It includes habits and choices that can reduce risk before disease starts. Some risks can be changed, and others cannot. The transcript describes common prevention strategies such as avoiding tobacco, limiting sun exposure, and making healthy lifestyle choices. These choices matter because they can help protect cells from damage over time. Prevention also includes knowing and reducing exposure to things that may...

cancer therapies

Cancer Treatment Options

Cancer treatment options include several ways to target cancer cells and help control the disease. Common approaches include chemotherapy, radiation therapy, surgery, and immunotherapy. Each method works in a different way, so doctors may choose one treatment or combine several. Chemotherapy uses drugs to kill fast-growing cells or stop them from dividing. Radiation therapy uses high-energy beams to damage cancer cells. Surgery removes a tumor when it can be reached safely. Immunotherapy helps...

targeted cancer therapies

How Targeted Cancer Drugs Work

Targeted cancer therapies use medicines that act on specific molecules linked to cancer cell growth. These drugs are designed to interfere with signals that help cancer cells survive and divide. The goal is to affect cancer cells more directly than many traditional treatments. The transcript highlights two examples of targeted therapy. Imatinib mesylate works by blocking a protein target involved in cancer growth. Trastuzumab is another targeted drug used in cancer treatment. These therapies...

Some cancers resist treatment and keep growing even after therapy. This video focuses on why that happens and how resistance changes cancer care. Treatment resistance can develop when cancer cells survive drugs that should destroy them. The cells may avoid the drug’s effects, or they may keep dividing after treatment starts. This makes the cancer harder to control. Understanding treatment-resistant cancer helps explain why some therapies work at first and then lose effect. It also shows why...

combination therapies and personalized medicine

combination-therapies-and-personalized-medicine

Personalized Cancer Treatment with Drug Combinations

Personalized cancer treatment uses drug combinations to better match therapy to a patient’s tumor. It brings together combination therapies and personalized medicine to improve how doctors choose treatment. Combination therapy means using two or more drugs at the same time or in sequence. This approach can help target cancer cells in more than one way and may reduce the chance that the tumor becomes resistant to one drug. Personalized medicine uses information about the patient and the tumor...

key terms and concepts

Learn why some cancers resist treatment and keep growing after therapy. Explore how drug resistance can make cancer harder to control.

Why Some Cancers Resist Treatment | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Why Some Cancers Resist Treatment

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