Somatic cancers are caused by mutations that occur in the DNA after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. They occur in the genomes of all dividing cells, both normal and neoplastic. They may occur as a result of misincorporation during DNA replication or through exposure to exogenous or endogenous mutagens. These alterations can (but do not always) cause cancer or other diseases.
There are two main classifications of lung cancer: small cell lung cancer and non-small cell lung cancer (NSCLC). Both types of cancers are treated differently. NSCLC begins in the epithelial cells. Adenocarcinoma starts in cells that produce mucus. Squamous cell carcinoma begins in the cells that line the airways. Large cell carcinoma begins in cells other than the two types described above.
There are multiple genes that may be changed, called mutations, in a lung tumor that drive the cancer. These mutations are not inherited or passed down to children instead they are restricted only to the patient. Mutations that are known to drive lung cancer may occur on one or more of several genes, including EGFR, ALK, KRAS, BRAF, HER2, ROS1, and RET. Testing the tumor for all these genes can be done by MSl and OncoCEPT-Solid.
|Afatinib (Gilotrif)||EGFR (HER1/ERBB1), HER2 (ERBB2/neu)||Non-small cell lung cancer (with EGFR exon 19 deletions or exon 21 substitution (L858R) mutations)||Afatinib (Gilotrif)|
|Alectinib (Alecensa)||ALK||Non-small cell lung cancer (with ALK fusion)||Alectinib (Alecensa)|
|Atezolizumab (Tecentriq)||PD-L1||Urothelial carcinoma Non-small cell lung cancer||Atezolizumab (Tecentriq)|
|Brigatinib (Alunbrig)||ALK||Non-small cell lung cancer (ALK+)||Brigatinib (Alunbrig)|
|Certinib (Zykadia)||ALK||Non-small cell lung cancer (with ALK fusion)||Ceritinib (Zykadia)|
|Crizotinib (Xalkori)||ALK, MET, ROS1||Non-small cell lung cancer (with ALK fusion or ROS1 gene alteration)||Crizotinib (Xalkori)|
|Dabrafenib (Tafinlar)||BRAF||Non-small cell lung cancer (with BRAF V600E Mutations)||Dabrafenib (Tafinlar)|
|Erlotinib (Tarceva)||EGFR (HER1/ERBB1)||Non-small cell lung cancer (with EGFR exon 19 deletions or exon 21 substitution (L858R) mutation)||Erlotinib (Tarceva)|
|Gefitinib (Iressa)||EGFR (HER1/ERBB1)||Non-small cell lung cancer (with EGFR exon 19 deletions or Geftinib (Iressa) exon 21 substitution (L858R) mutations)||Geftinib (Iressa)|
|Necitumumab||EGFR (HER1/ERBB1)||Squamous non-small cell lung cancer||Necitumumab (Portrazza)|
|Osimertinib (Tagrisso)||EGFR||Non-small cell lung cancer (with EGFR T790M mutation)||Osimertinib (Tagrisso)|
|Trametinib (Mekinist)||MEK||Non-small cell lung cancer (with BRAF V600E mutation)||Trametinib (Mekinist)|
Genes analyzed EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, ERBB2, PIK3CA
Immunotherapy companion diagnostic FDA approved Biomarkers-PDL1 (22C3 – DAKO, SP263,SP142 – Ventanna) by IHC
Our body’s immune system detects Infected cells and tumour cells and eliminated by cytotoxic T lymphocytes. Normal cells differentiate themselves by expressing a protein signal called PD-L1 to limit harm to surrounding tissue (programmed death ligand 1). This PD-L1 signal is a stop sign meant to prevent cytotoxic T cells from destroying normal cells. T cells use a receptor called PD-1 to identify the PD-L1 signal (programmed death receptor 1). Some tumours can also express the PD-L1 signal in order to deceive the immune system and avoid being detected. Anti-PD-1 therapy works by preventing the interaction between PD-1 and PD-L1 of tumour cells. Patient response from anti-PD-1 therapy (immunotherapy) is associated with PD-L1 expression. Different clones of PDL1 are validated against different targeted immunotherapies and hence specific PDL1 clone is to be requested for IHC test based on Targeted immunotherapeutic drugs for eg. PDL1 22C3 for Pembrolizumab.
3. Alk by IHC
Alk (D5F3), companion diagnostic, Ventana plateform- FDA approved molecular biomarker test by IHC
Screening for anaplastic lymphoma kinase (ALK) rearrangements is a very important process in treatment decision making for advanced non-small-cell lung cancer (NSCLC). This particular clone has high sensitivity and Specificity than other detection methods. The clone D5F3 recognizes the carboxyl terminus of human ALK protein.
The above accreditations have been granted to NEUBERG SUPRATECH REFERENCE LABORATORIES PRIVATE LIMITED (NSRL). The Neuberg Center for Genomic Medicine (NCGM) is affiliated to NSRL.