The Best Results So Far in Targeted Cancer Treatments: The ProfiLER Study

Targeted cancer treatments can improve survival and quality of life in patients for whom genetic testing identifies a meaningful molecular target. The ProfiLER study, presented at ASCO 2017, is the most current and comprehensive study of targeted cancer treatment efficacy.

The research included patients with low 5-year survival expectations and advanced colon (large bowel), breast, brain, head and neck cancer patients, patients with gynecological cancers and soft tissue sarcomas. Tumor samples underwent genetic testing, and in %52 of tumors, targetable DNA damage was found. Patients subsequently received targeted treatment.

At the end of the research, approximately %54 of patients receiving targeted therapy were alive after 3 years and approximately %35 after 5 years.

In patients not receiving targeted therapy, these rates were approximately %46 and %28, respectively. The same study found average time without disease progression of approximately 3 months. In addition, %24 of patients had no progression for 6 months.

What does this study mean clinically?

• Targeted therapies are among the most important steps in developing the personalized medicine model. A marked increase in survival was observed in patients receiving targeted treatment.
• Targeted treatment options in clinical use are quite limited. Discovering new-generation biomarkers in cancer and identifying genetic differences specific to particular cancers will accelerate targeted drug discovery.
• The tools determining which patient group should receive targeted drugs are genetic tests. However, results differ between testing centers, and reliability problems occur. Consequently, many patients either cannot benefit from targeted therapies or receive the wrong treatment.
• Planning targeted treatments requires, together with molecular genetics specialists, multidisciplinary work . .

What Is a Targeted Drug?

Targeted cancer treatment targets particular proteins, genes or tissues that allow cancer to survive and progress. Because these treatments target only cancer-related cellular events, normal cells and tissues suffer little harm. However, they cannot yet be used in every patient or cancer type. Patients’ health, the rate of cancer progression and suitability for clinical applications play important roles in whether targeted treatments can be administered.

There Are Two Types of Drugs for Targeted Cancer Treatment:

1) Monoclonal Antibodies: Monoclonal antibodies bind to antigens on cancer cells and activate the immune system. They can bind to receptors or to ligands that activate receptors, neutralizing them. Monoclonal antibodies act on cancer cells in 3 ways.

• Activating the immune system to attack the tumor cell
• Binding to molecules (ligands) or receptors responsible for cancer cell growth and multiplication to inhibit tumor growth and spread
• Carrying toxins/drugs to directly destroy cancer cells

2) Small-Molecule Inhibitors: They prevent uncontrolled proliferation by targeting proteins or enzymes in intracellular signaling pathways in cancer cells. Small-molecule inhibitors are generally taken orally and have short half-lives. They are less selective than monoclonal antibodies.

The diagram below shows some targeted drugs in clinical use for cancer and their mechanisms