Lung cancer is no longer just one disease. For many years, we spoke about small cell and non-small cell lung cancer (NSCLC). We now know that it is very important to distinguish two different histological types of NSCLC – squamous and non-squamous cell cancers as they have different characteristics, different oncogenic drivers causing different responses to various therapeutic agents. Chemotherapy with Bevacizumab or Pemetrexed is not indicated for squamous histology; on the other hand, Ipilimumab or Necitumumab seem to be more effective in squamous cell histology.

Understanding better the tumor cell biology, oncogenic drivers, signalling pathways and their interactions, and effect of the environment and immune system on a cancer cell behaviour now enables us to conduct research in order to inhibit (block) a specific receptor-pathway on an individual basis. In patients with non-squamous histology, we now routinely check for EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase) mutations as we have specific therapeutic agents to offer our patients which demonstrate significantly better efficacy and lower toxicity, when compared with the standard chemotherapy regimens such as platinum doublets for first-line treatments of metastatic NSCLC with the specific EGFR or ALK mutations. We have gained over the last years, experience regarding the development of resistance in the tumours treated with specific targeted agents. The different clonal changes are being expressed at the different metastatic sites, stressing the importance of the tumor in homogeneity and the importance to re-biopsy the tumor at the time of disease progression in order to understand the need for a specific agent to be administered in the next line of treatment.The necessity of an adequate tissue biopsy at the time of diagnosis cannot be stressed enough.

As we discover more oncogenic drivers and will have available therapies to inhibit them, more testing will need to be performed on each tumour in order to individualize the therapies. The testing will have to be rapid in order to prevent the patient’s deterioration while waiting for the results.

Immunotherapy will also play an important role in the treatments of lung cancer. Stimulating patients’ immune system by different vaccines or inhibiting the existing immunosuppression will be an important component of the fight against lung cancer. We will have to know how to combine different therapeutic agents in order to increase their efficacy, yet prevent toxicities and fight the development of resistance. The proper sequencing of various anticancer agents or regimens will be very important too.

The role of the microenvironment of lung cancer cells (fibroblasts, macrophages, immune system, etc.) is becoming more obvious now and is becoming an important player which will need to be addressed in our future trials and treatments.

As we discover more new targets and have more treatment options with the targeted therapies and immunotherapies, we hope to replace the traditional chemotherapy agents or chemotherapy regimens. The treatments in future will be given on an individualized personalized basis, in each line of treatment. By this approach, we hope to improve not only efficacy of the treatments and patients’ survival, but also their disease-related symptoms and quality of life (QOL). For the patients who know that their disease cure is unlikely, the toxicity of the treatments and adverse events, symptom improvements or delays of symptom deterioration and improvement of global health-related QOL are of the utmost importance. These promising new targeted therapies will enable us to make all of it a reality with a personalized approach to this very complex disease called lung cancer.

By Dr. Vera Hirsh, McGill University Health Centre (MUHC) Royal Victoria Hospital, Montreal, Canada