Is resistance to targeted therapy in cancer inevitable?
Lorey K Smith1, Karen E Sheppard2, Grant A McArthur1
1The Peter MacCallum Cancer Centre, Melbourne, 3000 VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, 3052 VIC, Australia.
Cancer Cell
|August 10, 2021
Abstract:
Resistance to targeted therapies is a major challenge in cancer care and occurs via genetic and non-genetic mechanisms. In this issue of Cancer Cell, Marin-Bejar et al. demonstrate that melanomas recurrently select genetic or non-genetic resistance trajectories and that targeting neural crest stem cell-like cells prevents non-genetic, but not genetic, resistance.
Insights
Melanoma develops resistance to targeted cancer therapies through genetic or non-genetic pathways. Targeting neural crest stem cell-like cells can prevent non-genetic resistance but not genetic resistance.
Area of Science:
- Oncology
- Cancer Biology
- Genetics
Background:
- Targeted therapies are crucial in cancer treatment but face significant challenges due to acquired resistance.
- Resistance mechanisms can be genetic (mutations) or non-genetic (epigenetic or cellular state changes).
Purpose of the Study:
- To investigate the recurrent resistance trajectories in melanoma.
- To determine the efficacy of targeting neural crest stem cell-like cells in preventing melanoma resistance.
Main Methods:
- Analysis of melanoma samples to identify genetic and non-genetic resistance mechanisms.
- Experimental models to test the impact of targeting neural crest stem cell-like cells on therapy resistance.
Main Results:
- Melanomas exhibit recurrent selection of distinct genetic or non-genetic resistance pathways.
- Targeting neural crest stem cell-like cells effectively prevents non-genetic resistance.
- Targeting neural crest stem cell-like cells does not prevent genetic resistance.
Conclusions:
- Melanoma resistance to targeted therapies is driven by distinct, recurrent trajectories.
- Neural crest stem cell-like cells are key mediators of non-genetic resistance, offering a potential therapeutic target.
- Genetic resistance mechanisms remain a significant challenge, requiring alternative therapeutic strategies.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
8.0K
The targeted cancer therapies, also known as “molecular targeted therapies,” 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...
There are several types of targeted therapies against...
8.0K
02:56Treatment Resistant Cancers
3.5K
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...
3.5K
02:50Combination Therapies and Personalized Medicine
5.3K
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 single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.3K
02:40Cancer Stem Cells and Tumor Maintenance
5.1K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.1K
02:53Adaptive Mechanisms in Cancer Cells
6.0K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.0K
02:49Cancer Therapies
8.7K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
8.7K