DNA Cancer Treatment: How It Targets Cancer’s Genetic Code

Deoxyribonucleic acid (DNA) is the instruction manual for every cell, containing the genetic code that dictates function, growth, and division. When errors, known as mutations, arise in this code, they can lead to the uncontrolled growth that characterizes cancer. This understanding of how specific DNA changes fuel the disease has paved the way for treatments that target the unique genetic makeup of cancer cells.

Cancer’s Blueprint: How DNA Changes Drive the Disease

The human genome is organized into chromosomes, which house thousands of genes that provide recipes for cellular proteins. A cell becomes cancerous from an accumulation of mutations in its DNA. These changes can take several forms:

• Point mutations, where a single DNA letter is incorrect.
• Insertions, where extra DNA is added.
• Deletions, where DNA is removed.
• Translocations, where DNA is moved to another part of the genome.

Certain genes are consequential when mutated. Proto-oncogenes are normal genes that help cells grow, but mutations can turn them into “oncogenes,” which act like a stuck accelerator pedal instructing the cell to multiply endlessly. An example is the MYC gene, which, when altered, can drive unregulated cell growth and tumor formation.

Conversely, tumor suppressor genes act as the brakes by slowing cell division, repairing DNA mistakes, or signaling cell death. For these genes to lose their function, both copies within a cell must be inactivated, a concept known as the “two-hit hypothesis.” The p53 gene is a tumor suppressor that is damaged or missing in a majority of cancers.

Epigenetic modifications can also contribute to cancer. These alterations do not change the DNA sequence but affect how genes are expressed. For example, hypermethylation can silence tumor suppressor genes, removing their protective function without a mutation.

Traditional Treatments: Attacking Cancer Cell DNA

Traditional cancer treatments like chemotherapy and radiation therapy work by inflicting widespread damage on the DNA of rapidly dividing cells. Because cancer cells replicate much faster than most normal cells, they are more vulnerable to these DNA-damaging attacks, which are designed to lead to cell death.

Chemotherapy uses a range of drugs to disrupt the cancer cell’s life cycle by targeting its DNA. Some classes, like alkylating agents, damage the DNA structure to prevent it from being copied correctly. Other types, such as topoisomerase inhibitors, interfere with enzymes necessary for untangling DNA during replication, causing breaks in the DNA strands that cannot be easily repaired. If the harm is extensive, this damage triggers cell self-destruction.

Radiation therapy operates on a similar principle, using high-energy waves or particles to damage cancer cell DNA. This can happen directly by physically breaking DNA strands. It can also occur indirectly when radiation creates reactive molecules called free radicals from water within the cell, which then attack the DNA.

These traditional methods are not selective and damage any rapidly dividing cell. This is why they cause side effects like hair loss and nausea, as they affect healthy cells in hair follicles and the digestive tract.

Precision Strikes: Targeting Specific DNA Flaws in Cancer

Precision medicine is a tailored approach to cancer treatment that recognizes each person’s cancer has a unique genetic signature. Instead of the broad assault of traditional therapies, precision medicine uses drugs designed to attack specific molecular targets driving the cancer’s growth. This allows for treatment that is matched to the specific genetic profile of a tumor.

The first step is genomic profiling, where a tumor sample is analyzed through DNA sequencing to create a map of its genetic alterations. This can be done on tumor tissue or through a “liquid biopsy,” which analyzes circulating tumor DNA (ctDNA) found in the blood. This profile reveals biomarkers that can serve as targets for therapy.

For example, some non-small cell lung cancers are driven by a mutation in the EGFR gene. EGFR inhibitors are drugs that block the overactive signaling from this mutated protein, halting the cancer’s growth. Similarly, about half of all melanomas have a BRAF V600E mutation, and BRAF inhibitors can shut down the pathway this mutation activates.

PARP inhibitors are another example, effective in cancers with BRCA1 or BRCA2 gene mutations, common in certain breast, ovarian, and prostate cancers. Cells with BRCA mutations have a faulty DNA repair system. PARP inhibitors block a different repair pathway, eliminating the backup mechanism and causing cancer cells to die from accumulated DNA damage, a concept called synthetic lethality.

The Next Wave: Advanced DNA-Informed Cancer Therapies

Building on precision medicine, the next generation of cancer treatments involves the direct use of genetic material. These advanced therapies use DNA not just as a target but as a tool to fight cancer from within the body’s own systems. These approaches are highly personalized and leverage genetic engineering to create “living drugs” or to train the immune system.

One example is CAR T-cell therapy. In this treatment, a patient’s T-cells are collected and genetically engineered in a lab to create a “chimeric antigen receptor” (CAR) on their surface. This new receptor is designed to recognize and bind to a protein on the patient’s cancer cells. This modification turns the T-cells into targeted cancer killers before they are infused back into the patient.

Therapeutic mRNA cancer vaccines are another approach. These vaccines deliver a piece of messenger RNA (mRNA) into the body’s cells. This mRNA instructs the cells to produce specific proteins found on tumor cells, known as antigens. The immune system then recognizes these antigens as foreign and learns to identify and attack the cancer.

Researchers are also exploring oncolytic viruses, which are genetically modified to selectively destroy cancer cells while leaving healthy cells unharmed. As the virus replicates, it bursts the cancer cell, releasing more virus to infect nearby cancer cells. Additionally, gene-editing technologies like CRISPR-Cas9 are being investigated to directly correct cancer-causing mutations or to engineer more effective immune cells.