Drugs used for lung cancer Flashcards
What are the types of non-small cell lung cancer?
1) Adenocarcinoma (the most common type of primary lung cancer, from the mucus-making cells)
2) Squamous cell cancer (often due to smoking)
3) Large cell carcinoma (cells look large and rounded)
- they behave similarly and respond to treatment in a different way to small cell lung cancer
What is small cell lung cancer SCLC?
- It is named like this under the microscope the cancer cell looks small and filled with the nucleus
- Usually due to smoking
What are the drugs used for lung cancer?
1) Antibiotics
- Doxorubicin
2) Microtubule inhibitor
- Paclitaxel (Taxol)
- Vincristine
3) Alkylating agents
- Cyclophosphamide and ifosfamide
4) Others
- Cisplatin & Carboplatin
- Etoposide
Which antibiotic is used for the treatment of lung cancer?
Doxorubicin
Which microtubule inhibitor is used for lung cancer?
1) Paclitaxel (Taxol)
2) Vincristine
Which alkylating agent is used for lung cancer?
1) Cyclophosphamide
2) Ifosfamide
What are the other agents used for lung cancer?
1) Cisplatin
2) Carboplatin
3) Etoposide
When do we perform lung surgery for lung cancer?
- We do not perform surgery for SCLC but we can perform it in the early stage of NSLC
- Patients with localized NSCLC are best treated with surgery
What are the indications for radiotherapy?
1) Radiotherapy for NSLC
- Patients with localized NSCLC are best treated with surgery, however many of them are inoperable due to comorbidities like smoking, in these situations, radiation therapy can be used (If NSCLC patients are inoperable due to any cause, we opt for radiotherapy)
2) Radiotherapy for SCLC
- Radiotherapy with chemotherapy is the treatment of choice for limited-stage SCLC
- SCLC patients who respond to therapy should also receive prophylactic cranial irradiation (PCI), which treats micrometastatic disease in the CNS (improves cure rates for limited-stage disease and prolongs survival for extensive-stage disease)
When do we perform genetic testing?
When the histology results are not of squamous cell histology (adenocarcinoma and large cell), tissue should be sent for genetic analysis of EGFR mutations, ALK rearrangement, and other mutations (essential for targeted treatment)
What are the different mutant lung cancer?
1) Adenocarcinoma
2) Large cell cancer
What are the different mutations of NSLC (non-squamous)?
1) EGFR: Epidermal growth factor receptor (TK receptor) MUTATION
2) KRAS mutations
3) ALK (Anaplastic lymphoma kinase) tyrosine kinase mutation
4) ROS1 mutation
5) BRAF V600E mutation
How do these mutations cause lung cancer?
1) these proteins are essential to regulating cellular proliferation and survival.
2) Under normal conditions, these proteins respond to external signals that control cell division and apoptosis, thereby maintaining tissue homeostasis. However, when these proteins acquire specific mutations, they can become constitutively active, meaning they are permanently “on” regardless of external signals.
3) In their mutated form, these tyrosine kinases continually signal the cell to divide, even when division is not needed, causing continuous signaling disrupting the normal cell cycle regulation, leading to unchecked cell proliferation.
What is the function of the EGFR-Tyrosine kinase receptor?
- EGFR belongs to the tyrosine kinase receptor (TKR) family
- Binding of a ligand like the EGF will induce a conformational change which facilitates the homo/heterodimer formation
- Activated EGFR will then phosphorylate its substrates, activating multiple downstream pathways within the cell (like PI3K-AKT “Involved in cell survival”, RAS-RAF-MEK-ERK “Involved in cell proliferation)
- In tyrosine kinase mutation, the signal is always “ON”, so we have continuous proliferation and survival of cells causing cancer
10-15% of NSCLC patients have mutations in which gene?
Exon 19/21 of the EGFR gene
What are the drugs given for patients with mutation in EGFR gene?
- EGFR TKIs
1) Gefitinib
2) Erlotinib
3) Afatinib
Which drug is given For resistant tumors with the T790M substitution?
Osimertinib (Osimertinib is a third-generation, orally bioavailable, irreversible inhibitor of T790M-mutant EGFR)
What is the KRAS mutation?
- Mutations in the gene that encodes for the KRAS protein, found in about 30% of NSCLC
- KRAS mutation is the commonest mutation in NSCLC
- KRAS mutation leads to an unrestrained growth and proliferation of cancer cells
- Mutated KRAS are very difficult to handle (we do not use drugs or monoclonal antibodies, rather mRNA vaccines)
What is the treatment for KRAS mutations?
- mRNA vaccines & pembrolizumab
- The patient’s cells are used to create a personalized vaccine against the cancer of the same patient
- Vaccines use tumor mRNA to instruct cells to produce antigens
- We present the antigens to the immune system stimulating it to recognize and target the KRAS-mutant cancer cells
- The body’s T-cells will start producing antibodies against the tumor antigens. Thereby, we use another drug to increase and strengthen the immune system response: pembrolizumab
- Pembrolizumab is an immune checkpoint inhibitor that helps boost the immune response by preventing cancer cells from evading immune detection
- Moderna is designed as an mRNA vaccine to generate and present KRAS neoantigens (proteins) to the immune system, which is intended to test alone and in combination with Merck’s KEYTRUDA (pembrolizumab)
