Smart Drugs in Cancer Treatment

21.03.2024

SMART DRUGS USED IN CANCER TREATMENT

Smart drug therapy refers to drugs that work by targeting specific molecules on the cancer cell. This method may have fewer side effects than traditional medications because it is less likely to damage healthy cells. Smart cancer drugs target specific proteins or genetic mutations that promote the growth and spread of cancer cells and work by killing cancer cells or stopping their growth. Smart drug therapy can also be personalized according to the genetic structure of the patient or the characteristics of the disease, which can increase the effectiveness of the treatment. This treatment method has an important place especially in cancer research and has started to be used in more and more types of cancer in recent years. The development of smart drugs enables more effective and target-oriented treatment of diseases.

Image 1: Nowadays, cancer treatments are increasingly coming down to the molecular level and the number of smart drugs in cancer treatment is increasing day by day.

WHICH RECEPTORS DO SMART DRUGS TARGET?

Smart drugs used in cancer treatment generally target specific receptors or proteins involved in pathways that control the growth and spread of cancer cells. Here are some important examples:

HER2 Receptors:Drugs that target the Human Epidermal Growth Factor Receptor 2 (HER2) receptor are targeted therapies used in some other types of cancer, especially HER2-positive breast cancer. These drugs bind to the HER2 protein and inhibit its activity to prevent the growth and spread of cancer cells. Some important drugs that target the HER2 receptor include:

• Trastuzumab: It is used to treat HER2-positive cancers, including breast cancer as well as some stomach cancers.

• Pertuzumab: It is effective in the treatment of HER2-positive breast cancer, usually used together with trastuzumab.

• Ado-trastuzumab emtansine: This drug, created by adding a chemotherapy drug to trastuzumab, is used especially in the later treatment lines of HER2-positive breast cancer.

• Lapatinib: It is used alone or in combination with HER2-positive breast cancers, usually in cases resistant to trastuzumab

• Neratinib: It can be used in early stage HER2-positive breast cancer, especially after trastuzumab treatment.

• Tucatinib: It is used in the treatment of advanced or metastatic HER2-positive breast cancer in patients who have developed resistance to other HER2-targeted treatments.

EGFR (Epidermal Growth Factor Receptor): Drugs that target the EGFR receptor are targeted therapies used especially in some lung cancers and colorectal cancers. Mutations of the EGFR receptor can lead to the growth and spread of cancer cells. Drugs targeting EGFR inhibit the growth of cancer cells by blocking the signaling pathways of this receptor. Some important drugs that target the EGFR receptor include:

• Erlotinib, Gefitinib, Afatinib: It is used in lung cancers with positive EGFR mutation.

• Osimertinib: It is effective in EGFR T790M mutation-positive advanced lung cancers. This drug can also be used in patients who have developed resistance to previously used EGFR inhibitors.

• Cetuximab: It is especially used in colorectal cancers and head and neck cancers. This drug binds to the outer surface of EGFR, blocking its activity.

• Panitumumab: It is used in metastatic colorectal cancer, especially in patients without RAS gene mutation (wild-type).

ALK (Anaplastic Lymphoma Kinase): Drugs that target the ALK receptor are used especially in cancer types such as some lung cancers that carry an ALK gene mutation or rearrangement. ALK-positive cancers grow and spread due to abnormal function of this gene. By blocking this activity, ALK inhibitors stop or slow the growth of cancer cells. Some important drugs that target the ALK receptor include:

• Crizotinib: It is used in ALK positive advanced lung cancers.

• Ceritinib: It is used in patients who are resistant to or intolerant to crizotinib.

• Alectinib: It is effective in both crizotinib-resistant and treatment-naïve ALK-positive lung cancer patients.

• Brigatinib: It is another ALK inhibitor that is effective against the resistance that develops after crizotinib.

• Lorlatinib: It is a newer drug used for cases where resistance has developed to other ALK inhibitors.

VEGF (Vascular Endothelial Growth Factor): Drugs targeting the VEGF receptor are used especially in cancer treatment by blocking the blood vessel formation (angiogenesis) of tumors. Inhibition of the VEGF pathway restricts tumor nutrition and growth and thus may slow or stop cancer progression. Some important drugs that target the VEGF receptor include:

• Bevacizumab: It is used in various types of cancer, especially colorectal, lung, breast and renal cell cancers.

• Aflibercept: It is used in the treatment of metastatic colorectal cancer and some eye diseases.

• Sorafenib: It is used in the treatment of renal cell carcinoma and hepatocellular carcinoma (liver cancer). It has several different targets besides VEGF.

• Sunitinib: It is used in types of cancer such as renal cell carcinoma and gastrointestinal stromal tumors (GIST).

• Pazopanib: It is used in renal cell carcinoma and soft tissue sarcomas.

BRAF Mutations: Mutations in the BRAF gene play an important role, especially in melanoma and some other types of cancer. Drugs that target the BRAF mutation attempt to stop the growth and spread of cancer cells by blocking the abnormal activity of the protein caused by this mutation. The main drugs that target BRAF mutation are:

• Vemurafenib: It is generally used in the treatment of BRAF V600E mutation-positive melanoma.

• Dabrafenib: Similar to vemurafenib, it is effective in treating BRAF V600E mutation-positive melanoma.

• Encorafenib: It is another option used in the treatment of BRAF V600E or V600K mutation-positive melanoma.

MEK (Mitogen-Activated Protein Kinase) inhibitors: It is used specifically in cancers with BRAF mutations and is often given in combination with BRAF inhibitors. MEK inhibitors target the MEK enzyme, which controls the growth and spread of cancer cells. These drugs may be especially effective in treating melanoma and some other types of cancer. The most commonly used MEK inhibitors are:

• Trametinib: It is especially used in the treatment of BRAF V600E or V600K mutation-positive advanced stage melanoma. It is often used in combination with a BRAF inhibitor such as dabrafenib.

• Cobimetinib: It is also used in the treatment of BRAF V600 mutation-positive melanoma and is often given together with vemurafenib.

• Binimetinib: It is used in the treatment of melanoma with BRAF V600 mutation and is often preferred in combination with encorafenib.

The use of MEK inhibitors depends on the molecular characteristics of the cancer, the patient's general health status, and previous treatments. It is important to closely monitor patients' side effects and response to treatment while using these medications. The treatment plan should be determined by a physician according to the specific situation of each patient.

PD-1/PD-L1 (Programmed Death 1/Programmed Death-Ligand 1): Drugs that target PD-1 and PD-L1 receptors belong to the immunotherapy class. These drugs prevent cancer cells from "disguising" themselves by inhibiting the immune system, thus helping the immune system recognize and destroy cancer cells. PD-1 and PD-L1 inhibitors may be effective in various types of cancer. Important drugs that target PD-1 and PD-L1 include:

• Nivolumab: It is a PD-1 inhibitor and is used in melanoma, lung cancer, renal cell carcinoma, head and neck cancers, Hodgkin lymphoma, and some other types of cancer.

• Pembrolizumab: It is a PD-1 inhibitor and is used in melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, Hodgkin lymphoma, urothelial carcinoma, and some other types of cancer.

• Atezolizumab: It is a PD-L1 inhibitor and is used in urothelial carcinoma (bladder cancer) and non-small cell lung cancer.

• Durvalumab: It is a PD-L1 inhibitor and is used especially in non-small cell lung cancer and bladder cancer.

• Cemiplimab: It is a PD-1 inhibitor and is used in the treatment of metastatic or locally advanced segmented cell skin cancer.

These drugs play an important role in cancer treatment and, as part of personalized medicine, can be selected based on the patient's specific genetic makeup and the characteristics of his cancer. Still, the use and selection of these medications should be evaluated by a healthcare professional based on each patient's condition and the characteristics of his or her cancer.

Image 2: Smart drugs target molecules involved in cancer cell growth and proliferation.

WHAT ARE THE ADVANTAGES?

Smart drug therapy in cancer has many benefits. This treatment approach offers some important advantages over traditional chemotherapy methods:

Targeted Therapy: Smart drugs recognize specific targets (receptors, genetic mutations, etc.) found in cancer cells and work against these targets. This allows the treatment to affect only cancer cells and cause minimal damage to healthy cells.

Less Side Effects: Unlike traditional chemotherapy, side effects are generally fewer because smart drugs cause less damage to healthy cells. This may enable patients to have a better quality of life during treatment.

Personalized Treatment: Smart drug therapy can be personalized based on the patient's genetic makeup and the characteristics of his cancer. This increases the effectiveness of the treatment and helps determine the most appropriate treatment method for each patient.

Decreased Development of Resistance: Cancer cells can develop resistance to traditional chemotherapy over time. Because smart drugs work on more specific targets, this can prevent the development of resistance or reduce the impact of resistance.

Control of the disease and increased recovery rates: Smart drugs can control the growth and spread of cancer cells more effectively. This slows or stops the progression of the disease in some cases and can increase recovery rates.

Combined Treatment Possibilities: Smart drugs can be used in combination with other treatment methods (radiation, surgery, other drug treatments), which can increase the overall effectiveness of the treatment.

Despite these advantages, the effectiveness of smart drug therapy may vary depending on the type of cancer, its stage, and the patient's overall health status. Therefore, each patient's treatment options should be evaluated by an oncologist.

Image 3: Smart cancer treatments are also being developed in different cancer treatment branches such as nuclear medicine.

IN WHICH CANCERS IS IT USED?

Smart drugs in cancer are used in various types of cancer. Some common types of cancer for which these drugs are used include:

Breast Cancer: HER2-positive breast cancer, in particular, is an important type of cancer targeted by smart drugs. Drugs such as trastuzumab and pertuzumab are used in this type.

Lung cancer: Smart drugs are especially effective in EGFR mutation-positive or ALK-positive lung cancers. Erlotinib, gefitinib and crizotinib are drugs used in this type of cancer.

Colorectal Cancer: EGFR-targeting drugs (e.g., cetuximab and panitumumab) and VEGF inhibitors (e.g., bevacizumab) are used in colorectal cancer.

Melanoma: BRAF or MEK inhibitors are used to treat melanoma. Drugs such as vemurafenib and dabrafenib are effective in BRAF mutation-positive melanoma patients.

Lymphoma and Leukemia: Some smart drugs are particularly effective in chronic myeloid leukemia (CML) and some types of lymphoma. While imatinib is used to treat CML, rituximab is used in some types of lymphoma.

Prostate cancer:Drugs that target hormone receptors are used specifically to treat advanced or metastatic prostate cancer.

Pancreatic Cancer:Some targeted therapies have begun to be used in the treatment of pancreatic cancer, but research is still ongoing in this area.

Liver Cancer: Sorafenib is a smart drug used in the treatment of liver cancer.

Kidney Cancer: In renal cell cancer, drugs targeting VEGF and mTOR pathways (sunitinib, pazopanib) are used.

Head and Neck Cancers: EGFR inhibitors may also be effective in this type of cancer.

The use and choice of smart drugs depends on the patient's genetic and molecular profiling, the stage of the cancer, and other health conditions. The use of smart drugs in cancer treatment has been a significant development in recent years, and this approach has significantly changed treatment strategies. Smart drugs work by targeting cancer cells and provide treatment for specific molecular structures or genetic anomalies of these cells. These drugs target specific receptors or genetic mutations that prevent cancer cells from growing and spreading. Smart drugs, unlike traditional chemotherapy, have the potential to cause less damage to healthy cells, contributing to reducing side effects and improving patients' quality of life. However, the use of these drugs requires a customized approach depending on the type of cancer, its stage, and the patient's general health condition. To maximize the effectiveness of treatment and minimize side effects, patients' condition and response to treatment should be closely monitored by a healthcare professional.