The Era of Personalized Cancer Treatment Is Truly Beginning

One of the most striking medical innovations since 2000 is the concept of personalized treatment. What does it mean? Is it science fiction or reality? Is a new drug produced for every patient? What does treatment based on a tumor’s genetics involve? This article examines whether personalized treatment is possible and what it means.

What Is Personalized Cancer Treatment?

Personalized cancer treatment aims to identify the most appropriate treatment by considering each patient’s genetic, biological, and personal characteristics. It uses next-generation genetic and genomic tests to understand cancer’s complex structure and identify the approaches producing the best treatment response.

Is Cancer a Genetic Disease?

Cancer is a genetic disease at the cellular level. It results from accumulated genetic damage causing uncontrolled cell proliferation. However, its genetic nature does not mean it is inherited. Cases passed down from parents are hereditary cancer cases and account for only 10% of all cancers. The remaining 90% arise from genetic changes occurring later in life. Genetic testing is therefore extremely important in cancer.

What Is a Genetic Test, and How Is It Performed?

Genetic tests detect specific variations in a person’s DNA. Performed on tumor tissue and, more recently, blood or saliva samples, they focus on identifying DNA changes or mutations. Thousands of types exist today. Common methods include Next-Generation Sequencing (NGS), Polymerase Chain Reaction (PCR) and immunohistochemical studies. These tests play a major role in diagnosing and managing genetic diseases.

The 2 Main Types of Genetic Tests in Cancer

Genetic tests serve two main purposes in cancer treatment:

• Detecting Cancer-Driving Genetic Changes in Tumors: these tests detect sporadic genetic changes not inherited from parents to assess suitability for targeted cancer drugs. For example, EGFR, ALK, HER2, NTRK, and BRAF alterations are examined. Initially performed on tumor tissue, these tests are now also performed using blood samples.
• Detecting Hereditary Cancer Gene Changes: in people with a family history of cancer, inherited gene changes (such as BRCA 1-2 mutations) are identified to calculate individual and familial risk. This helps early diagnosis and assesses suitability for drugs targeting hereditary cancer genes (PARP inhibitors).

Toward Personalized Treatment: Why Now?

Personalized cancer treatment has become a frequently discussed scientific concept in recent years. This innovative approach has developed over the past 20 years through major projects such as the Human Genome Project and The Cancer Genome Atlas. These important projects have given it an increasingly prominent place in medical literature. However, only recently has truly comprehensive implementation become possible. Why now?

Rapid genetic and genomic advances, molecular biology breakthroughs, and bioinformatics innovations make personalized treatment possible. Advanced molecular tests, particularly Next-Generation Sequencing (NGS), can analyze cancer’s genetic profile in detail, making it easier to offer the most suitable options to each patient. More precise, individualized approaches are consequently being adopted.

Tests and Approaches Used in Personalized Cancer Treatment

Personalized cancer treatment uses the most advanced technologies available in modern medicine. Important tests and methods enabling it include:

1. Genomic Tests for Targeted Therapies

Understanding cancer’s genetic structure is the most important step in personalizing treatment. This starts by identifying cancer-driving mutations. Detecting the genetic changes causing cancer helps determine which targeted drugs the disease may respond to. Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) tests measure the extent of mutations and genomic changes in a tumor. They are critical to predicting immunotherapy effectiveness because the amount and type of genetic changes strongly affect treatment response.

2. Hereditary Cancer Panel Tests

Used to detect familial cancers, these tests play an important role in identifying inherited risk factors, enabling early diagnosis and preventive measures in people with a family history.

3. Recurrence Score Tests

These genetic signature tests assess recurrence risk after cancer treatment, identifying patients who truly need chemotherapy, particularly after early breast cancer. The best known is Oncotype Dx. Predicting the likelihood of recurrence enables more effective management. Additional measures can be taken for high-risk patients, while those at low risk can avoid unnecessary chemotherapy.

4. Minimal Residual Disease (MRD) Tests

Minimal residual disease tests detect cancer cells remaining after treatment, revealing residual disease and enabling more accurate assessment of treatment response. Prominent examples are Natera’s Signatera and Guardant’s Reveal tests.

5. Multicancer Early Detection (MCED) Tests

Early detection is vital in cancer treatment. MCED (Multi-Cancer Early Detection) tests detect various cancers at an early stage, enabling quicker treatment. They generally use a simple blood sample and search for biological traces of cancer. Laboratory analysis detects abnormal biomarkers such as DNA or proteins. No MCED test has yet received FDA (US Food and Drug Administration) approval, but testing continues in hundreds of thousands of people in clinical trials. These tests are expected to become a major topic in oncology.

6. Anticancer Agent Sensitivity Tests

These tests assess cancer cells’ sensitivity to specific anticancer drugs to identify the most effective agents. Living tumor tissue obtained through biopsy is grown in laboratory culture, then its response to different cancer drugs is measured. This can help identify the most suitable drugs and combinations for patients.

7. Pharmacogenetic Tests

Predicting drug adverse effects and effectiveness from patients’ genetic characteristics, these tests provide information on widely used chemotherapies such as 5FU and irinotecan, particularly their adverse effects. They thereby guide drug selection during treatment.

8. Microbiome Tests

These tests examine how microorganisms in the body affect cancer treatment and play an important role in the treatment process. Microbiome balance may affect patients’ treatment response.

9. Polygenic Risk Scores (PRS)

Calculating the combined effect of multiple genetic factors, polygenic risk scores determine individual cancer risk, helping develop personal risk profiles and preventive measures.

10. Radiogenomic Tests

Genetic sensitivity to radiotherapy and pharmacotherapy is assessed using radiogenomic tests,which guide treatment planning. By predicting responses to radiation and certain drugs, they help determine the most appropriate strategies.

Personalized Cancer Drugs and Living Drugs

Another important dimension of personalized cancer treatment is drugs developed according to the patient’s genetic profile and the tumor’s biological characteristics. Notable advances include CAR T-cell therapy, TIL (tumor-infiltrating lymphocyte) therapy, and mRNA cancer vaccines.

CAR T-Cell Therapy

CAR T-cell therapy genetically reprograms the patient’s own T cells to recognize and destroy cancer cells. This immunotherapy has received FDA approval after showing effectiveness in many leukemias and lymphomas, offering a personalized approach.

TIL (Tumor-Infiltrating Lymphocyte) Therapy

TIL therapy is another living drug introduced for some cancers, such as the aggressive skin cancer melanoma. T cells isolated from tumor tissue are expanded in a laboratory and returned to the patient, where they help control disease by attacking cancer cells. In February 2024, TIL therapy received approval for melanoma as the first living drug to achieve this landmark.

mRNA Cancer Vaccines

Known worldwide through the COVID-19 pandemic and closely associated with Turkish scientists Uğur Şahin and Özlem Türeci, mRNA technology also has considerable potential in cancer treatment. mRNA cancer vaccines produce tumor-specific proteins to activate immunity against cancer cells. By targeting cancer cells, they aim to stop disease progression and occupy an important place among personalized treatment options.

These innovative therapies aim to expand personalized cancer treatment’s possibilities, improve quality of life, and make treatment more effective.

Toward Personalized Cancer Treatment: A Vision for the Future

Personalized cancer treatment extends beyond genetic testing to a holistic approach considering biological and personal factors. It aims for greater treatment success and improved quality of life with fewer adverse effects. Genetic tests using comprehensive, diverse technologies personalize treatment, offering the most suitable methods to each patient.

As these methods develop and become more widespread, personalized cancer treatment is expected to become standard practice.