Novel Targets, Novel Treatments: The Changing Landscape of Non-Small Cell Lung Cancer

Abstract

Treatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift. Once a disease with limited potential therapies, treatment options for patients have exploded with the availability of molecular testing to direct management and targeted therapies to treat tumors with specific driver mutations. New in vitro diagnostics allow for the early and non-invasive detection of disease, and emerging in vivo imaging techniques allow for better detection and monitoring. The development of checkpoint inhibitor immunotherapy has arguably been the biggest advance in lung cancer treatment, given that the vast majority of NSCLC tumors can be treated with these therapies. Specific targeted therapies, including those against KRAS, EGFR, RTK, and others have also improved the outcomes for those individuals bearing an actionable mutation. New and emerging therapies, such as bispecific antibodies, CAR T cell therapy, and molecular targeted radiotherapy, offer promise to patients for whom none of the existing therapies have proved effective. In this review, we provide the most up-to-date survey to our knowledge regarding emerging diagnostic and therapeutic strategies for lung cancer to provide clinicians with a comprehensive reference of the options for treatment available now and those which are soon to come.

Keywords: PET imaging; lung cancer; molecular diagnostics; targeted therapies.

Figure 1

Demonstrates the leading risk factors for lung cancer in the United States.

Figure 2

Demonstrates a 62-year-old woman with biopsy-proven left lung adenocarcinoma. (A) Axial CT showing part-solid pulmonary nodule in the left lower lobe, with biopsy demonstrating adenocarcinoma (Stage: T1N1M0). (B) MIP, (C) CT and (D) fused ¹⁸F FDG-PET/CT maximum intensity projection showing radiotracer avid lung malignancy and uptake in a left hilar node, indeterminate on prior CT, and confirmed as nodal metastasis on subsequent biopsy.

Figure 3

Demonstrates a 68-year-old man with biopsy-proven right lung adenocarcinoma (Stage: T3N3M0). (A) Axial CT showing a mass in the lateral right lower lobe, abutting adjacent pleura, with biopsy demonstrating adenocarcinoma. (B) ¹⁸F-FDG-PET/CT maximum-intensity projection and (C,D) fused images showing multiple enlarged, avid ipsilateral and contralateral mediastinal and supraclavicular lymph nodes, suspicious for metastases, with the left supraclavicular node subsequently biopsied confirming malignancy.

Figure 4

Demonstrates a 68-year-old man with biopsy-proven left lung squamous cell carcinoma (Stage: T4N2M1c). (A) ¹⁸F-FDG-PET/CT maximum intensity projection showing left lower lobe perihilar neoplasm invading the mediastinum, narrowing the left main bronchus with post-obstructive atelectasis; a biopsy demonstrated squamous cell carcinoma. (B–D) CT images and (E–G) fused images demonstrate enlarged FDG-avid subcarinal node suspicious for metastasis and multiple FDG-avid osseous lesions, with some lytic, and others CT-occult, consistent with metastases.

Figure 5

Is a representative ⁶⁸Ga-FAPI maximum intensity projection, negative for malignancy, showing the physiologic uptake of this tracer.

Figure 6

Overview of the available imaging and therapy options for patients with NSCLC. Treatment now includes chemotherapy, radiation therapy, targeted therapy, and immunotherapy. PET imaging and molecular radiotherapy targets include FDG, FLT, FAP, PD-1, PD-L1, integrins, and fMISO.