Lung Cancer is the leading cause of cancer death among both men and women globally. Tobacco smoking is the most prominent cause of lung cancers but not the only cause. The majority of lung cancers include small cell lung cancer (SCLC) and the three non-small cell lung cancer (NSCLC) types. NSCLC tumours are highly heterogenous and despite advances in therapy, the overall 10 year survival rate remans low at 8%.

Lung cancer is the leading cause of cancer mortality worldwide, with about 1.8 million deaths in 2020. About 85% of cases are non-small cell lung cancer (NSCLC), with lung adenocarcinoma and lung squamous cell carcinoma being the prevalent sybtypes. The majority of patietns present with stage III-IV disease, with limited treamtent options and survival rates. (Gilligan, “Residual ctDNA after treatment predcits early relapse in patients with early-stage non-small cell lung cancer” March 2022, Annals of Oncology). 

Diagnosis: 

Usually lung cancer is initially viewed on chest X-rays or CT scans which is then confirmed with a biopsy. Four major histology types categorized by the size and appearance of malignant cells. 

Recent research has shown that cirulating tumour DNA (ctDNA) in blood can be used as a liquid biopsy, providing a minimally invasive diagnostic tool to assess tumour burden in cancer patients. Fragmetns of DNA are rleeased into the circulation as cell free DNA through apoptosis, necrosis or active release. In cancer patients, DNA is also released form tumour cells and this ctDNA may represent a small fraction of the total cell free DNA. (Gilligan, “Residual ctDNA after treatment predcits early relapse in patients with early-stage non-small cell lung cancer” March 2022, Annals of Oncology).

Treatment

Traditional Treatment Therapies:

NSCLC was the leading cause of cancer death in 2000, claiming more than 1 million lives. Traditional therapeutics towards SCLC lung cancer is chemotherapy and/or radiotherapy while patients with NSCLC a surgical resection of the primary tumour with or without a combination of chemotherapy and chest radiotherapy. Common chemotherapy regimens include cisplatin, platinum or carboplatin in combination with one or more of gemcitabine, paclitaxel, docetaxel, etoposide, vinorelbine, topotecan, or irinotecan. However, the average 5-year survival rate of lung cancer patients is less than 15%. The survival rate has not improved over the past decade, mainly because the tumors become resistant to traditional chemotherapy and the cancer is able to expand and metastasize. In addition, chemotherapy nonspecifically kills normal proliferating cells in addition to cancerous cells.

Unpredictability in Treatmnet of NSCLC:

A great majority of therapies for NSCLC failed in clinical trails. In non-small-cell lung cancer alone, between 1990 and 2005, a total of 1,631 new drugs were sutdied in phase II. Only sevel of these new agents gained FDA approval. OSI Pharmaceuticals, LLC v. Apotex Inc. (USPTO Patent Trial and Appeal Board IPR201601284)

Anti-EGFR compunds: Activation of the EGFR triggers a cascade of events leading to cell reprudction, and inhibiting EGFR can be beneficial in treating tumor cells. 

–Erlotinib (N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy-4-quinazo-linamine): is and FDA anti EGFR compound. It is protected by US Patent No: 6,900,221. 

PD-1 (programmed death receptor-1): Bristol Myers Squibb Company has obained FDA approval for Opdivo (nivolumab) injection, for intravenous use, for the treatment of maetastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

Keytruda (Merck) which is an anti-PD-1 blocking antibody is approved for patients with metastatic non-small cell lung cancer whose tumors express PD-1 and who have disease progression after platinum containing chemotherapy. 

Possible Treatments in Future: Recent evidence showed that cancer in general may be sustained by a small subpopulation of cancer stem cells (CSCs).

–CD133 has been identified as a surface marker of CSCs and methods of treating subjects by adminsitering compositions antgaonistics to this polypeptide have been proposed (WO 2010/126452). 

–Inhibitors of farnesyltransferase (FTIs) have been demonstrated to be effective in treating Ras-dependent tumors in animal models.