1. How dangerous lung cancer?

Lung cancer is a malignant disease of the lungs. About 85% - 90% of cases are related to smoking status (active or passive). According to statistics, every year around the world there are about 2.09 million new cases and 1.76 million deaths from lung cancer. In 2018, Vietnam had more than 23,000 people with lung cancer, this number is likely to increase in the following years. Lung cancer is one of the most common cancers and has the second highest mortality rate after liver cancer.

Non-small cell lung cancer accounts for more than 80% of cases, including adenocarcinoma, squamous cell carcinoma and a small number of large cell cancers. Silent progression and poor prognosis are important features of this disease. Patients can come to the doctor because of prolonged cough, coughing up blood, shortness of breath, chest pain, bone pain...

Meanwhile, more than 50% of patients when diagnosed are already at the metastatic stage, ie the cells Cancer cells have spread to the lungs and other organs of the body and the prognosis for these cases is very low, only about 6%.

Targeted therapy is an effective treatment method for patients with metastatic lung cancer to help relieve symptoms, improve quality of life, slow tumor progression and prolong survival. extra for the patient.

2. What is targeted therapy?

One of the most basic features of cancer cells is the presence of mutations in genes responsible for cell growth (called oncogenes). Targeted therapy is a method of targeting specific molecules required for carcinogenesis and tumor growth (oncogenes and the proteins produced by these oncogenes); acts on receptors located on the cell membrane or in the cell. 

Monoclonal antibodies: are targeted therapies that act on receptors on the extracellular portion of the cell membrane.

Small molecule medicines: Acts on receptors from within the cell. These drugs are intended for groups of patients with genetic mutations with specific biomarkers.

3. Drugs used in targeted therapies for lung cancer

3.1 Monoclonal antibodies

Bevacizumab is a monoclonal antibody that binds to VEGF (vascular endothelial growth factor: vascular endothelial growth factor) to prevent VEGF-mediated activation of tyrosine kinase receptors is essential for angiogenesis. Bevacizumab is used in combination with chemotherapy, with immunotherapy. Note: Bevacizumab is indicated for first-line treatment in patients with non-small cell lung cancer who have no prior history of hemoptysis.

Ramucirumab is a recombinant monoclonal antibody that binds to the VEGF receptor Ramucirumab is a first-line treatment in a group of NSCLC lung cancer patients with EGFR mutations. Since 2020, Ramucirumab/Erlotinib has been indicated for the first-line treatment of patients with NSCLC lung cancer with EGFR mutations.

Cetuximab monoclonalantibody that binds to EGFR. Cetuximab in combination with chemotherapy (Cisplatin/vinorebine) also helps to achieve overall survival, however, due to its high leukopenia toxicity, it is not widely recommended.

3.2 Small Molecular Weight Drugs

Thanks to the development of science and technology, it is now possible to identify certain gene mutations for the use of specific targeted drugs. Mutations in genes often cause cancer to grow and metastasize. Targeted drugs help block mutated genes, stopping tumor growth and shrinking tumors.

According to research and statistical reports, about 20% of lung cancer patients are caused by mutations in 1 of 5 genes EGFR, ALK, ROS1, BRAF and KRAS. Therefore, in studying the selection of targeted therapeutic drugs in the treatment of lung cancer, FAD also distinguishes each type of lung cancer drug according to different gene mutations.

3.3 Targeted therapies EGFR

EGFR gene mutations

For lung cancer, mutations in the EGFR gene (Epideral growth factor receptor - epidermal growth factor receptor) were the first approved and currently still targeted therapies. continues to be studied to this day.

This is the most common type of gene mutation in lung cancer patients, especially in Asian populations, female patients, non-smokers, and lung cancer origin. According to a study in Vietnam, for every 100 lung cancer patients, 32 people carry mutations in the EGFR gene.

In 1986, researchers Stanley Cohen and Rita Levi-Montalcini were awarded the Nobel Prize in Medicine for their discovery of growth factors, including EGF (epidermal growth factor). Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor. The outer part of the cell membrane is the place for the EGFs to attach to form a complex, thereby activating a series of intracellular signaling pathways to help cells grow and multiply.

There are many types of EGFR mutations detected, but about 90% of cases are deletion mutations on exon 19 and point mutations on exon 21-L858R.

When mutations in the EGFR gene occur, these tyrosine kinase receptors by themselves are able to activate the intracellular pathway without the need for EGF binding, leading to disorganized proliferation of cancer cells. letters.

Current drugs to target EGFR :

1st generation drugs include Erlotinib and Gefitinib. Both drugs have similar therapeutic effect, helping to improve quality of life, increase tumor response rate, and prolong disease progression-free time by 5 - 6 months compared with chemotherapy. The advantage of this group of drugs is safety, few side effects, mainly skin rash if using erlotinib or increased liver enzymes if using gefitinib.

The second-generation drug class is Afatinib. According to the study, Afatinib is highly effective in groups with brain metastases and groups with rare mutations such as L861Q, G719X and S768I. In addition to the strengths mentioned, the use cases of 2nd generation drugs often suffer from more toxicity (such as diarrhea, skin rash, enteritis, dermatitis) and those toxicity are usually of high level. more severe than the 1st generation

The 3rd generation drugs include osimertinib. Osimertinib also has the ability to inhibit the activity of EGFR mutations in a sustainable, irreversible way. In particular, it can also inhibit mutations in the T790M gene. This is a type of gene mutation that increases the likelihood of treatment failure. It occurs in about 50% - 60% of cases of non-small cell lung cancer patients treated with drugs targeting 1st or 2nd generation EGFR after 9 - 12 months.

Conclusion: Lung cancer remains a major challenge for clinicians. Targeted therapy has opened a new era in the treatment of advanced non-small cell lung cancer, helping to prolong survival and improve patients' quality of life. Even now, cost is still a barrier to patient access. But hopefully in the future, there will be many new gene mutations discovered, lower drug prices to bring more treatment opportunities and benefits to patients.

Source: National Cancer Institute