Erlotinib, sold under the brand name Tarceva among others, is a medication used to treat non-small cell lung cancer (NSCLC) and pancreatic cancer. Specifically it is used for NSCLC with mutations in the epidermal growth factor receptor (EGFR) — either an exon 19 deletion (del19) or exon 21 (L858R) substitution mutation — which has spread to other parts of the body. It is taken by mouth.
Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively and postoperatively.
KRAS is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide (proliferate) or to mature and take on specialized functions (differentiate). It is called KRAS because it was first identified as a viral oncogene in the KirstenRAt Sarcoma virus. The oncogene identified was derived from a cellular genome, so KRAS, when found in a cellular genome, is called a proto-oncogene.
Combined small cell lung carcinoma is a form of multiphasic lung cancer that is diagnosed by a pathologist when a malignant tumor, arising from transformed cells originating in lung tissue, contains a component of small cell lung carcinoma (SCLC) mixed with one or more components of any histological variant of non-small cell lung carcinoma (NSCLC) in any relative proportion.
Treatment of lung cancer refers to the use of medical therapies, such as surgery, radiation, chemotherapy, immunotherapy, percutaneous ablation, and palliative care, alone or in combination, in an attempt to cure or lessen the adverse impact of malignant neoplasms originating in lung tissue.
Targeted therapy of lung cancer refers to using agents specifically designed to selectively target molecular pathways responsible for, or that substantially drive, the malignant phenotype of lung cancer cells, and as a consequence of this (relative) selectivity, cause fewer toxic effects on normal cells.
Adenocarcinoma of the lung is the most common type of lung cancer, and like other forms of lung cancer, it is characterized by distinct cellular and molecular features. It is classified as one of several non-small cell lung cancers (NSCLC), to distinguish it from small cell lung cancer which has a different behavior and prognosis. Lung adenocarcinoma is further classified into several subtypes and variants. The signs and symptoms of this specific type of lung cancer are similar to other forms of lung cancer, and patients most commonly complain of persistent cough and shortness of breath.
ALK inhibitors are anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4-ALK translocation. They fall under the category of tyrosine kinase inhibitors, which work by inhibiting proteins involved in the abnormal growth of tumour cells. All the current approved ALK inhibitors function by binding to the ATP pocket of the abnormal ALK protein, blocking its access to energy and deactivating it. A majority of ALK-rearranged NSCLC harbour the EML4-ALK fusion, although as of 2020, over 92 fusion partners have been discovered in ALK+ NSCLC. For each fusion partner, there can be several fusion variants depending on the position the two genes were fused at, and this may have implications on the response of the tumour and prognosis of the patient.
ALK positive lung cancer is a primary malignant lung tumor whose cells contain a characteristic abnormal configuration of DNA wherein, most frequently, the echinoderm microtubule-associated protein-like 4 (EML4) gene is fused to the anaplastic lymphoma kinase (ALK) gene. Less frequently, there will be novel translocation partners for the ALK gene, in place of EML4. This abnormal gene fusion leads to the production of a protein that appears, in many cases, to promote and maintain the malignant behavior of the cancer cells.
Sir Bruce Anthony John Ponder FMedSci FAACR FRS FRCP is an English geneticist and cancer researcher. He is Emeritus Professor of Oncology at the University of Cambridge and former director of the Cancer Research UK Cambridge Institute and of the Cancer Research UK Cambridge Cancer Centre.
Brigatinib, sold under the brand name Alunbrig among others, is a small-molecule targeted cancer therapy being developed by Ariad Pharmaceuticals, Inc. Brigatinib acts as both an anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) inhibitor.
Squamous-cell carcinoma (SCC) of the lung is a histologic type of non-small-cell lung carcinoma (NSCLC). It is the second most prevalent type of lung cancer after lung adenocarcinoma and it originates in the bronchi. Its tumor cells are characterized by a squamous appearance, similar to the one observed in epidermal cells. Squamous-cell carcinoma of the lung is strongly associated with tobacco smoking, more than any other forms of NSCLC.
Lungscape is a translational research program designed, implemented and conducted by the European Thoracic Oncology Platform (ETOP) in collaboration with a series of leading hospitals and clinics across Europe and beyond.
Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).
Osimertinib, sold under the brand name Tagrisso, is a medication used to treat non-small-cell lung carcinomas with specific mutations. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor.
Rosalind Anne Eeles is a Professor of Oncogenetics at the Institute of Cancer Research and clinician at the Royal Marsden NHS Foundation Trust. She is a leader in the field of genetic susceptibility to prostate cancer, and is known for the discovery of 14 genetic variants involved in prostate cancer predisposition. According to ResearchGate, Eeles has published more than 500 articles in peer-reviewed journals, with over 34,000 citations and an h-index of 92. Eeles was elected a Fellow of the Academy of Medical Science in 2012. She was awarded a National Institute for Health Research Senior Investigator Emeritus in 2014.
Christine M. Lovly is an associate professor of medicine at Vanderbilt University. Her research involves the development of novel treatment strategies for ALK positive lung cancer.
RET kinase inhibitors are a type of targeted cancer treatment that block abnormally activated RET proto-oncogene, a protein involved in cell growth. These inhibitors are used to treat cancers like non-small cell lung cancer, medullary thyroid carcinoma, and some types of colorectal and pancreatic cancer.
Hereditary lobular breast cancer is a rare inherited cancer predisposition associated with pathogenic CDH1 (gene) germline mutations, and without apparent correlation with the hereditary diffuse gastric cancer syndrome. Research studies identified novel CDH1 germline variants in women with diagnosed lobular breast cancer and without any family history of gastric carcinoma. Firstly, in 2018 Giovanni Corso et al. defined this syndrome as a new cancer predisposition and the Authors suggested additional clinical criteria to testing CDH1 in lobular breast cancer patients. In 2020, the International Gastric Cancer Linkage Consortium recognized officially that the hereditary lobular breast cancer is a possible independent syndrome. To date, there are reported about 40 families clustering for lobular breast cancer and associated with CDH1 germline mutations but without association with diffuse gastric cancer. Other recent studies demonstrated a possible correlation between hereditary lobular breast cancer and gastric cancer risk.
Alberto Bardelli is an Italian geneticist and cancer researcher, expert in the field of precision medicine. He is a full professor of histology at the Department of Oncology, University of Turin and Scientific Director of IFOM, the AIRC Institute of Molecular Oncology.