Related Experiment Video
Updated: May 29, 2026
08:46
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Nucleic Acid Therapeutics for "Undruggable" Cancer Targets: Mechanisms, Challenges, and Prospects
Feng Xu1, Ke Wang2, Kaizhong Lu1
1Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China.
Summary
Nucleic acid therapeutics offer a new way to target difficult cancer oncoproteins like Ras, MYC, and p53. These therapies work at the mRNA and genomic levels, overcoming limitations of traditional drugs.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Key cancer oncoproteins (Ras, MYC, p53) are historically "undruggable" by conventional drugs.
- Traditional drugs require specific structural domains, which these targets lack.
- Precision oncology needs novel therapeutic strategies for these challenging targets.
Purpose of the Study:
- To review nucleic acid therapeutics for "undruggable" cancer targets.
- To examine mechanisms, translational progress, and challenges of nucleic acid modalities.
- To highlight future directions for targeting intractable oncoproteins.
Main Methods:
- Systematic review of nucleic acid therapeutics (ASOs, siRNAs, miRNAs, aptamers, mRNA vaccines).
- Analysis of mechanisms: transcript degradation, translational inhibition, regulatory interference.
- Critical evaluation of translational bottlenecks: delivery, safety, manufacturing.
Main Results:
- Nucleic acid therapeutics bypass protein structure limitations by targeting mRNA and genomic levels.
- Diverse modalities show promise against Ras, MYC, and p53.
- Nanocarrier platforms are advancing delivery efficiency and safety.
Conclusions:
- Nucleic acid therapeutics represent a paradigm shift in cancer treatment.
- These therapies enable precise regulation of historically "undruggable" cancer targets.
- Advances in technology and computational design will further enhance their potential.
Related Concept Videos
02:57Targeted Cancer Therapies
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 specific...
There are several types of targeted therapies against specific...
02:57Targeted Cancer Therapies
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 specific...
There are several types of targeted therapies against specific...
01:26Targets for Drug Action: Overview
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
02:56Treatment 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 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...
02:18Cancer
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
02:56Treatment 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...