C-MET inhibitors in the treatment of lung cancer.

OPINION STATEMENT: Lung cancer is the most common malignant neoplasm and constitutes the most common neoplastic cause of death globally. The results of therapies employing standard chemotherapy are unsatisfactory. Currently, efforts are being made to personalize the therapy; numerous clinical studies are being conducted around the world to assess the efficacy and safety of agents directed at molecular targets. One of these molecular targets is the c-MET proto-oncogene, whose primary ligand is hepatocyte growth factor (HGF). C-MET hyperactivity has been observed in numerous neoplasms, including non-small-cell lung carcinoma. Prolonged or continuous activity of the receptor leads to excessive cell proliferation and is related to the development or progression of neoplastic disease. C-MET inhibitors can be classified into three groups: small-molecule tyrosine kinase inhibitors of the c-MET receptor (crizotinib, tivantinib, cabozantinib, foretinib), as well as monoclonal antibodies against c-MET (onartuzumab) and against the HGF ligand (ficlatuzumab, rilotumumab). The efficacy and safety of these agents is assessed both in monotherapy and in combination with other molecularly targeted agents. Furthermore, the toxicity profile of c-MET inhibitors is completely different from that of standard chemotherapy. The best understood c-MET inhibitor used in the treatment of non-small-cell lung carcinoma patients is crizotinib. It is registered for patients with the presence of ALK gene rearrangements after the failure of the first line of treatment based on platinum derivatives. The purpose of this present paper is to present clinical studies that assessed the efficacy and safety of c-MET inhibitors for the treatment of non-small-cell lung carcinoma, as well as current indications for the use of these molecules.

Actual status of therapeutic vaccination in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related death worldwide. Although treatment methods such as surgery, radiotherapy and/or chemotherapy have improved, prognosis remains unsatisfactory, and developing new therapeutic strategies is still an urgent matter. Immunotherapy is a novel therapeutic approach wherein activated immune cells can specifically kill tumour cells. Several lung cancer vaccines have demonstrated prolonged survival time in phase II and III trials, and several clinical trials are under investigation. However, many clinical trials involving cancer vaccination with defined tumour antigens have shown this method to work only in a small number of patients. Cancer immunotherapy is not completely effective in eradicating tumour cells because they evade host immune control.

Anti-angiogenic agents in the treatment of non-small cell lung cancer.

Lung cancer is the most common malignant neoplasm diagnosed worldwide. In Poland, in 2011, lung cancer was diagnosed in 14,522 men and 6,283 women. Morbidity and mortality are nearly equal, and lung cancer is still the most common cause of cancer-related death among men as well as among women. Approximately 80% of lung cancer cases are non-small-cell lung cancer. The most commonly applied chemotherapy regimens do not produce satisfactory effects. Oncological research is now focused on molecular targeted therapies; immunotherapy is also under evaluation. The formation of abnormal blood vessels has an enormous impact on the development and progression of a tumor. Bevacizumab is a monoclonal antibody which binds VEGF (vascular endothelial growth factor). A different group of drugs is constituted by small-molecule antiangiogenic tyrosine kinase inhibitors. These agents represent a different profile of side effects in comparison to chemotherapy. The mode of action, differing from cytotoxic drugs, requires renewed analysis as well as standardization of radiological response assessment criteria.

EGFR gene mutations in patients with adenosquamous lung carcinoma.

AIM: Adenosquamous (ADSQ) carcinoma accounts for 1-4% of non-small cell lung cancer (NSCLC). The origin of ADSQ carcinoma and its genetic background is not fully understood. Most studies concerning epidermal growth factor receptor (EGFR) mutation status are performed in adenocarcinoma, while there is limited information about the prevalence of this mutation in ADSQ-bearing Caucasian patients and the efficacy of EGFR tyrosine kinase inhibitors. METHODS: EGFR gene status has been examined in 1000 non-squamous NSCLC patients of Polish origin. Polymerase chain reaction (PCR) followed by DNA fragment length analysis and allele-specific PCR as well as real-time PCR technique were used to estimate EGFR gene status. Complete clinical data were obtained for all examined patients. RESULTS: In the group of 1000 non-squamous NSCLC patients, ADSQ was diagnosed in 14 (1.4%) cases. Activating mutations of EGFR were observed in 28.6% (four out of 14) of ADSQ-bearing patients and included deletions of 15 base-pairs in exon 19 in three cases (one man and two women) and substitution of L861Q with coexistence of G719X mutation in one non-smoking male patient. Deletions were diagnosed in two non-smoking patients and one current-smoking female patient (50 pack-years). One non-smoking man with deletion in exon 19 of EGFR gene was successfully treated with gefitinib in first-line therapy. CONCLUSIONS: EGFR gene mutations in ADSQ carcinoma patients may be more common than previously thought. EGFR mutation testing is appropriate in ADSQ-bearing patients, in which response for molecular-based therapy is predictable.