Unraveling novel targets for lung squamous cell carcinoma

Aim/goals:

1. Sequence locally advanced early-stage patient’s tumors with squamous cell carcinoma tumors.
2. Test drug combinations inferred from sequencing data on patient-derived organoids and xenografts from those tumors.
3. Devise new therapeutic targets that could be tested in subsequent clinical trials.

 

Summary:

Lung cancer (LC) is the primary cause of cancer-related death around the world, accounting for over 28% of cancer-related mortality, more than breast, colon, prostate, and pancreas combined. While local treatments for non-small cell lung carcinoma (NSCLC; 85% of all forms of LC) are frequently effective, a high proportion of patients with potentially “curable disease” recur locally and/or distantly, and it is this metastatic progression that leads to death.

The most common subtypes of NSCLC are lung adenocarcinoma (LADC, ~50% of all NSCLC) and lung squamous cell carcinoma (LSCC, ~30% of NSCLC). Approximately 20% of LADC in Canada show driver mutations, such as EGFR, ALK and ROS1, and molecular therapeutics are clinically available to target these types of lung cancer. Such targeted therapies result in improved survival over standard chemotherapy along with a far more favorable side-effect profile. Such personalized therapies are lacking for patients with LSCC. This unmet need is the primary concern of this proposal. Of note, some Canadian populations have an even higher incidence, such as the Inuit, where approximately 40% of their population have LSCC.

We propose to sequence treatment naïve LSCC patients’ tumors to unravel novel targetable biomarkers and to test drug combinations (salvage therapies) inferred from the sequencing data on patient-derived organoids and xenografts from those patients. This will lead to new therapeutic targets that could be tested in subsequent clinical trials.