Research Progress of Molecular Target Therapy in Non-Small Cell Lung Cancer

In 2017 the first published PFS results of PACIFIC study demonstrated new opportunities of immunotherapy in locally-advanced unresectable non-small-cell lung cancer (NSCLC) after chemoradiation (CRT). The positive overall survival results in this trial were received next year. This trial has become the first positive study in the more then 10 years after failure of all trials which investigated different approaches for improvement efficacy of standard CRT (induction therapy, consolidation therapy, target therapy, increased RT dose). The PACIFIC trial has opened new opportunities to improve outcomes in this patient’s population. Durvalumab was registered in Russia in July 2019, however clinical experience of durvalumab administration is still limited and we need to build expertise in this field. In this article we present the first example of durvalumab therapy in post CRT period in Bashkortostan real clinical practices. Patient with IIIB st NSCLC started durvalumab therapy after standard CRT. The complete response was registered after 4 months of therapy and currently after 9 months of therapy it is still remain.

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Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer

Cells ◽

10.3390/cells10102620 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2620

Author(s):

Bin Wang ◽

Hanfei Guo ◽

Haiyang Xu ◽

Hongquan Yu ◽

Yong Chen ◽

...

Keyword(s):

Lung Cancer ◽

Central Nervous System ◽

Nervous System ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Research Progress ◽

High Morbidity ◽

Small Cell Lung ◽

Cns Metastasis

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors and has high morbidity and mortality rates. Central nervous system (CNS) metastasis is one of the most frequent complications in patients with NSCLC and seriously affects the quality of life (QOL) and overall survival (OS) of patients, with a median OS of untreated patients of only 1–3 months. There are various treatment methods for NSCLC CNS metastasis, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, which do not meet the requirements of patients in terms of improving OS and QOL. There are still many problems in the treatment of NSCLC CNS metastasis that need to be solved urgently. This review summarizes the research progress in the treatment of NSCLC CNS metastasis to provide a reference for clinical practice.

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Resistance to KRASG12C Inhibitors in Non-Small Cell Lung Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.787585 ◽

2021 ◽

Vol 11 ◽

Author(s):

Juan Bautista Blaquier ◽

Andrés Felipe Cardona ◽

Gonzalo Recondo

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Molecular Mechanisms ◽

Target Therapy ◽

Phase 1 ◽

Small Cell ◽

Small Cell Lung ◽

Intrinsic Resistance ◽

Secondary Resistance

KRAS mutations are one of the most prevalent oncogenic alterations in cancer. Until recently, drug development targeting KRAS did not convey clinical benefits to patients. Specific KRASG12C inhibitors, such as sotorasib and adagrasib, have been designed to bind to the protein’s mutant structure and block KRASG12C in its GDP-bound inactive state. Phase 1/2 trials have shown promising anti-tumor activity, especially in pretreated non-small cell lung cancer patients. As expected, both primary and secondary resistance to KRASG12C inhibitors invariably occurs, and molecular mechanisms have been characterized in pre-clinical models and patients. Several mechanisms such as tyrosine kinase receptors (RTKs) mediated feedback reactivation of ERK-dependent signaling can result in intrinsic resistance to KRAS target therapy. Acquired resistance to KRASG12C inhibitors include novel KRAS mutations such as Y96D/C and other RAS-MAPK effector protein mutations. This review focuses on the intrinsic and acquired mechanisms of resistance to KRASG12C inhibitors in KRASG12C mutant non-small cell lung cancer and the potential clinical strategies to overcome or prevent it.

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