New treatment modalities in lung cancer

Lung cancer is one of the top three most common types of cancer seen in both men and women. In cancer-related deaths, it ranks first both in men and women. The risk factor, which is much stronger than environmental (air pollution, passive smoking) and genetic factors, is the use of tobacco and tobacco products, according to experts. The increase in smoking, especially in younger age groups, increases the incidence of lung cancer. Another increase is observed during the pandemic. Since COVID-19 causes problems such as pneumonia in the lungs and increases the amount of tomographies taken in the hospitals, many lung cancer cases are diagnosed in this way. There are new methods for its treatment now.

Thanks to the recent technological and medical developments, lung cancer is no longer a type of cancer that is difficult to treat as it used to be. While the science world recognizes the tumor cell better through the new treatment methods it has developed and the innovative medical technologies it uses, we now achieve more successful results in lung cancer when compared to the past. In this issue of our journal, we wanted to discuss the latest developments in lung cancer treatments, which are handled from a multidisciplinary perspective, from the same perspective for the main topic. Recent developments in treatment of lung cancer mentioned by Prof. Necdet Üskent, MD. a medical oncologist at the Anadolu Medical Center and the Coordinator of Oncological Sciences and Prof. Hale Basak Caglar, MD. a radiation oncologist and the Director of the Radiation Oncology Department deserve a great appreciation regarding science.

THERE IS NO ESCAPE EVEN THEY ARE IN DORMANT MODE!

Cancer cells in dormant mode cannot evade science.

By taking advantage of evolutionary survival mechanisms, cancer cells can evade treatments such as chemotherapy that targets proliferating cells. To do this, they have the ability of dividing slowly, or even the non-interrupted dormant mode called the G0 phase. Cancer cells in dormant mode are not affected by chemotherapy and can mutate by developing drug resistance in dormant mode. Thus, the cells begin to divide again and continue to ensure the spread of the disease. This is the primary mechanism behind the reoccurrence of tumors that initially have reduced size with good response to chemotherapy.

As is often seen in breast and lung cancers, a cancer cell that has been dormant for years can suddenly take action. Dormant cancer cells consume their own cell components or their own proteins to survive (autophagy). However, science produced a cure also for this dormant mode of cancer cells. With new drugs that block autophagy, it is now possible to destroy dormant cancer cells as well.

IMMUNOTHERAPY

WARRIOR CELLS NOW RECOGNIZE THE ENEMY

Immunotherapy, which is based on directing immune system cells to tumor cells, is one of the important treatment approaches that have been studied for years. To avoid being caught by the immune system, cancer cells take advantage of a mechanism known as checkpoint molecules that prevent warrior cells (T-lymphocytes) from attacking normal body cells. Since cancer cells do not look any different from normal cells, warrior cells do not attack cancer cells they see as friends. However, with scientific studies since 2011, it has now become possible for warrior cells to bypass the checkpoint and attack cancer cells. 7 immunotherapy drugs, generally called “Immune Checkpoint Suppressants", are used successfully in many types of cancer, especially in lung cancer.

ADOPTIVE CELL THERAPY

It is a therapy based on placing some genetic materials into T-cells and giving them back to the patient after being reproduced in the laboratory in order to increase the recognition of cancer cells by immune cells.

Through this method, known as CAR-T cell therapy, significant successes have been achieved in resistant lymphomas and leukemias, and trials have also begun for lung cancers. These warrior T-cells, containing Chimeric Antigen Receptors (CAR), are able to recognize and destroy tumor-specific antigen.

TIL cell therapy is another type of treatment. TILs are lymphocytes that are collected around cancer cells. These cells are isolated from the person and activated to recognize the tumor in the laboratory and can be given back to the patient.

CANCER VACCINES AND PERSON-SPECIFIC VACCINES

If there is a recognizable antigen specific to that cancer on the surface of the cancer cell, it is possible to activate the body's immune system against that antigen. Vaccines developed against NeuGmc and EGFR antigens found on the cell surface in lung cancers are treatments used as maintenance therapy for selected cases whose tumor burden is reduced by chemotherapy, permitted by the ministries of health of some countries. In addition, Phase 1 and Phase 2 studies of various peptide vaccines and messenger-RNA vaccines are ongoing.

SMART DRUGS ARE IN ACTION!

SMART DRUGS FOR TUMOR-SPECIFIC MUTATIONS

Genetic changes, which are the target of treatment, are seen in the type of lung cancers, especially non-small cell “adenocarcinomas”. These changes, which are seen between 1 percent and 35 percent depending on the type of genetic mutations and changes, can usually be blocked with drugs in oral tablet form. Thus, the size of the tumor begins to be reduced rapidly as the genetic target that activates the tumor is eliminated. While the number of smart drugs that were previously directed only at genetic targets such as EGFR, ALK and ROS-1 is increasing, new targets are now being determined. In patients with special mutations, the tumor is controlled with these drugs even at advanced stages, and their life span is extended.

As explained at the last World Cancer Congress, survival rates are increasing with advances in lung cancer treatments. For example, survival rates in stage 3 were 2 years in the past, today they have extended to at least 5 years.

DEVELOPMENTS IN RADIATION ONCOLOGY

Targeted radiotherapy

Radiotherapy is an important part of today's current multidisciplinary cancer treatment. Also in lung cancer, radiotherapy has an important place in almost every stage of the disease. Radiotherapy has been used as a standard (in the form of radiosurgery) for many years in patients with stage 1 disease who cannot be operated for medical reasons or in cases where an operation is not desired. There are studies conducted in the scientific arena to answer the question of “Is the operation an additional option in stage I disease, or can radiosurgery achieve similar success?”. When these studies are concluded, maybe within 10 years, surgery and radiosurgery will be offered to patients as equal treatments before treatment.

If the tumor has been safely removed, no additional radiotherapy is required for operated patients. In stage 3 disease (locally advanced stage), radiotherapy as standard local treatment is a recommended method concomitant with chemotherapy. If a metastatic disease is present, it is the primary local treatment option used for the treatment of metastases.

In addition to the knowledge and experience of the specialist team, the devices used undoubtedly have a great share in the success of radiosurgery. Sensitive irradiating devices such as CyberKnife are used successfully in today's radiosurgery, and the use of respiratory control devices is also important, especially in lung cancer. As it is known, our lungs are the organs that move the most during respiration, and because of the respiratory movement in the lungs, irradiation to tumors that do not stand still becomes difficult. By means of new generation respiratory control devices, the positions that tumor tissues change during respiration are calculated and irradiation can be made to the right point at the right time.

Prof. Hale Basak Caglar, MD. a radiation oncologist and the Director of the Radiation Oncology Department, says “It is very important to maintain the quality of life in radiotherapy.”

For this reason, it is always the first priority to initiate, administer and complete the most appropriate treatment as soon as possible, and to protect the patient from side effects in the best way possible”.