Modulating the gut microbiome in non-small cell lung cancer: Challenges and opportunities.

Despite the efficacy of immunotherapy in non-small cell lung cancer (NSCLC), the majority of the patients experience relapse with limited subsequent treatment options. Preclinical studies of various epithelial tumors, such as melanoma and NSCLC, have shown that harnessing the gut microbiome resulted in improvement of therapeutic responses to immunotherapy. Is this review, we summarize the role of microbiome, including lung and gut microbiome in the context of NSCLC, provide overview of the mechanisms of microbiome in efficacy and toxicity of chemotherapies and immunotherapies, and address current ongoing clinical trials for NSCLC including fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs).

Management of HER2 alterations in non-small cell lung cancer - The past, present, and future.

HER2 mutations, which account for 2-4% of non-small cell lung cancer (NSCLC), are distinct molecular alterations identified via next generation sequencing (NGS). Previously, treatment outcomes in HER2-mutant metastatic NSCLC were dismal, showing limited clinical benefit with platinum-based chemotherapy with or without immunotherapy. In contrast to HER2-altered breast and gastric cancer, HER2-mutant NSCLC does not benefit from HER2 targeting agents such as trastuzumab or TDM1. HER2 mutations are also inherently different from HER2 overexpression and amplification. Currently, trastuzumab deruxtecan, a HER2 targeting antibody drug conjugate (ADC) is the first and only approved treatment option for patients with HER2-mutant metastatic NSCLC after failure with standard treatment. In this review, we summarized the biology of HER2 and detection of HER2 overexpression, amplification and mutations, as well as general landscape of landmark and ongoing clinical trials encompassing from chemotherapy to targeted agents, including tyrosine kinase inhibitors (TKIs), ADCs and investigational agents.