Targeted Therapy

Cancer cells require specific molecules (also referred to as “proteins”) to grow and multiply. These molecules are typically created by cancer cells or by cancer-causing genes. Targeted therapies “target” these molecules, or the genes that create these molecules, to slow or stop cancer growth. Patients’ blood or tumor tissue are typically tested to determine if any of these molecules are present prior to initiating treatment with a targeted therapy.

Targeted therapies can be given alone or in addition to chemotherapy or radiation therapy. These treatments can be administered orally (usually as a pill) or intravenously. There are two broad types of targeted therapies – small molecule drugs and monoclonal antibodies. Small molecule drugs are small enough to enter directly into cancer cells and interfere with molecules inside the cells. Monoclonal antibodies are proteins that attach to targets found on the outer membrane of cancer cells and interfere with cancer-causing molecules through various mechanisms.

Current molecular targets in lung cancer:

• Immune system – Cancer cells have developed mechanisms to evade and “hide” from the body’s immune system. Targeted therapies can “mark” cancer cells so that they can be identified by the immune system for destruction. Targeted therapies can also attach themselves to cancerous lymphocytes and deliver cytotoxic chemotherapy directly into the cell. Additionally, targeted therapies can help boost the body’s immune system through the activation of “T cells” to better identify and destroy the cancer.
  • Immune system targeted therapies used in lung cancer:
    • Nivolumab (Opdivo®)
    • Pembrolizumab (Keytruda®)
    • Atezolizumab (Tecentriq®)
    • Durvalumab (Imfinzi®)
    • Ipilimumab (Yervoy®)
    • Cemiplimab (Libtayor®)
• Angiogenesis – Cancer needs a blood supply to deliver nutrients so that the cancer cells can grow and replicate. Angiogenesis is a process through which new blood vessels are formed to help “feed” the tumor. Cancer cells release a signal called vascular endothelial growth factor (VEGF) to induce angiogenesis. Targeted therapies can block VEGF, thus starving the cancer of its nutrient blood supply.
  • Angiogenesis (VEGF) targeted therapies used in lung cancer:
    • Bevacizumab (Avastin®)
    • Ramucirumab (Cyramza®)
• Cell growth – Cancer cells can grow rapidly through complex molecular pathways. In these pathways, enzymes called “tyrosine kinases” play an important role in a cell signaling cascade that controls cell growth, replication, and destruction. Tyrosine kinase inhibitors (TKI’s) have been developed to interfere with tyrosine kinase signaling, thus slowing or stopping cancer cell growth and replication, or inducing cell destruction. Tyrosine kinases targeted in lung cancer include EGFR, ALK, ROS1, BRAF/MEK, NTRK, and MET. The following are current TKI inhibitors approved by the FDA for lung cancer.
  • MET inhibitors:
    • Capmatinib (Tabrecta®)
    • Tepotinib (Tepmetko®)
  • EGFR, Exon 19 Deletion or Exon 21 L858R Mutation inhibitors:
    • Afatinib (Gilotrif®)
    • Dacomitinib (Vizimpro®)
    • Erlotinib (Tarceva®)
    • Gefitinib (Iressa®)
    • Osimertinib (Tagrisso®)
  • EGFR Exon 20 Insertion inhibitors:
    • Amivantamab-vmjw (Rybrevant®)
  • ALK inhibitors:
    • Alectinib (Alecensa®)
    • Brigatinib (Alunbrig®)
    • Crizotinib (Xalkori®)
    • Ceritinib (Zykadia®)
    • Lorlatinib (Lorbrena®)
  • ROS1 inhibitors:
    • Ceritinib (Zykadia®)
    • Crizotinib (Xalkori®)
    • Entrectinib (Rozyltrek®)
    • Lorlatinib (Lorbrena®)
  • BRAF/MEK inhibitors:
    • Dabrafenib (Taflinar®)
    • Trametinib (Mekinist®)
  • NTRK inhibitors:
    • Entrectinib (Rozyltrek®)
    • Larotrectinib (Vitrakvi®)
  • RET inhibitors:
    • Selpercatinib (Retevmo®)
    • Pralsetinib (Gavreto®)
  • KRAS G12C inhibitors:
    • Sororasib (Lumakras®)