Lung cancer is a leading cause of death worldwide, accounting for nearly 1.80 million deaths in 2020. It is the most common cancer in both sexes with 2.21 million new cases diagnosed in 2020. Nevertheless, in the past few years, most Western countries have recorded a decline in lung cancer morbidity and mortality according to the American Cancer Society. This achievement is largely due to the institution of enhanced strategies for the prevention, screening, early diagnosis, and treatment of same. In contrast, lung cancer incidence is still increasing in most low- and middle-income countries, due to a lack of access to early diagnosis and treatment. Comprehensive treatment is reportedly available in more than 90% of high-income countries but less than 15% in low-income countries.

Lung cancer is made up of a group of molecularly and histologically heterogeneous subtypes, which are classified as either non-small cell lung cancer (NSCLC; 85%) or small cell lung cancer (SCLC; 10-15%). Appropriate treatment is based on whether the tumor is NSCLC or SCLC, as well as its stage and molecular characteristics. Despite the advancement in treatment, lung cancer still has a poor prognosis and the lowest 5-year survival rate as compared to the other cancer sites. Multiple factors are responsible for this, including cigarette smoking, sociodemographic factors, abnormal progression of the disease such as metastasis, and resistance to currently available anticancer therapies. For instance, 80% of lung cancer deaths in the United States are still caused by cigarette smoking. Moreover, most patients in underserved communities are diagnosed at an advanced stage after the initiation of metastasis. These geographic disparities in disease occurrence will probably worsen the overall survival rate of lung cancer patients.

The problem of drug resistance caused by single-drug chemotherapy has increased in recent years. By comparison, combination therapy, the use of more than one type of therapy in treating a patient, is a hallmark of cancer treatment. However, multiple drugs may increase the risk of drug interactions. To address this potential risk and elevate the likelihood treatment will be effective, chemotherapy is sometimes used along with immunotherapy, immunotherapy with anti-vascular targeting, immunotherapy with radiotherapy, immunotherapy with immunotherapy, etc.

Since chemotherapy drugs affect cancer cells at different points in the cell cycle, using a combination of drugs increases the chance that all of the cancer cells will be eliminated.

The complexity of the disease – its tendency to spread beyond its original site and become resistant to certain drugs, and its genetic diversity – underscores the need for a variety of approaches to attack it. In many cases, combination therapy not only increases the chances of a cure or long-term remission but also reduces damage to vital organs and tissues more than a single approach.

This Research Topic aims to review the current state-of-the-art strategies in lung cancer therapy and provide updates on the combination therapy. This topic, therefore, covers cutting-edge research, review articles, editorials, and correspondence from experts in the field of clinical, translational, and basic science in lung malignancies including but not limited to the following topics:

• Combination therapies

• Combination chemotherapy

• Antiangiogenic therapy

• Chemo-immunotherapy

• Immune checkpoint inhibitors

• Chemoradiotherapy

• Targeted therapy

• New Lung cancer treatment

Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.

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