Clinical significance of <i>BIM</i> deletion polymorphism in chemoradiotherapy for non‐small cell lung cancer

Wakabayashi, Yu; Masuda, Takeshi; Fujitaka, Kazunori; Nakashima, Toshikatsu; Okumoto, Joe; Shimoji, Kiyofumi; Nishimura, Y.; Yamaguchi, Kakuhiro; Sakamoto, Shinjiro; Horimasu, Yasushi; Miyamoto, Shintaro; Iwamoto, Hiroshi; Ohshimo, Shinichiro; Hamada, Hironobu; Hattori, Noboru

doi:10.1111/cas.14711

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…Recent evidence also shows that selective targeting of these pathways has cytotoxic effects on cancer stem cells (See Table 2). (Bolomsky et al, 2020) Bcl family proteins/gene silencing (i) Bcl-2 siRNA and antisense nucleotides (Gagliardi and Ashizawa, 2022;Meng et al, 2015) (ii) Bim-1 siRNA (Schwulst et al, 2008;Wakabayashi et al, 2021) Targeting p53…”

Section: Drugs Targeting Autophagymentioning

confidence: 99%

Apoptosis and Autophagy: Therapeutic Implications in Cancer

Halder

2024

IJERR

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Despite the advances in the medical field so far, cancer remains a global health priority even now. Considering the drug resistance and the failure of cancer therapies to achieve complete eradication of cancer cells in certain populations, developing molecules that induce programmed cell death or apoptosis has been the focus of cancer research for several decades. Apoptosis evasion is one of the hallmarks of cancer cells, and efforts continue to achieve complete annihilation of cancer cells through selective killing. On the other hand, autophagy, a mode of cell degradation, is considered a double-edged sword. Recent studies show that autophagy also can be manipulated to selectively target cancer cells based on the tumor microenvironment and cellular context. Studies show that autophagy is an evolutionarily conserved process initiated during stress response and has enormous importance in maintaining physiological balance. Most importantly, the dynamic equilibrium between apoptosis and autophagy is crucial in maintaining cellular homeostasis. Although a ‘cell eating’ process, the fate of autophagic cells depends entirely on the nature of stress and the extent of crosstalk between autophagy. This understanding is of immense significance when designing therapeutic interventions targeting apoptosis and autophagy. Currently, several studies are ongoing to gain insights into the role of autophagy in cancer initiation, invasion, progression, angiogenesis, and metastasis. This review focuses on the two major cell death mechanisms, apoptosis and autophagy, in the context of cancer, their crosstalk, and the therapeutic interventions targeting both modes of cell death.

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Section: Drugs Targeting Autophagymentioning

confidence: 99%

Apoptosis and Autophagy: Therapeutic Implications in Cancer

Halder

2024

IJERR

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“…BIM, also known as B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11, encodes BCL2L11, which is a member of Bcl-2 protein family. BIM deletion polymorphism, resulting from the 2903-bp genomic deletion occurring in intron 2 of BIM gene, is commonly seen in East Asian and Hispanic patients with EGFR -mutant lung cancer with an incidence rate of 11.3–18.6% ( 8 , 9 ). Some studies reported that BIM deletion polymorphism predicted an unfavorable prognosis in EGFR -mutant NSCLC patients when treated with EGFR-TKIs ( 8 , 10 - 12 ), but other studies failed to find an association between the presence of BIM deletion polymorphism and the clinical outcome in these patients ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

“…BIM deletion polymorphism, resulting from the 2903-bp genomic deletion occurring in intron 2 of BIM gene, is commonly seen in East Asian and Hispanic patients with EGFR -mutant lung cancer with an incidence rate of 11.3–18.6% ( 8 , 9 ). Some studies reported that BIM deletion polymorphism predicted an unfavorable prognosis in EGFR -mutant NSCLC patients when treated with EGFR-TKIs ( 8 , 10 - 12 ), but other studies failed to find an association between the presence of BIM deletion polymorphism and the clinical outcome in these patients ( 13 , 14 ). Moreover, an array of studies have demonstrated that increased BIM at the RNA level enhances killing of NSCLC cells by the EGFR-TKIs, which contributes to the molecular mechanisms leading to tumor regression ( 15 - 18 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of osimertinib in a metastatic lung adenocarcinoma patient harboring somatic EGFR delL747_S752 and germline BIM deletion polymorphism: a case report and literature review

Zheng¹,

Niu²,

Zeng³

et al. 2022

Transl Cancer Res TCR

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Background: Epidermal growth factor receptor (EGFR) exon 19 deletion (19del) and the exon 21 L858R point mutation are the most established predictive factors for the efficacy of EGFR-tyrosine kinase inhibitor (TKI) in patients with non-small cell lung cancer (NSCLC). To date, more than 50 subtypes of EGFR 19dels have been documented in NSCLC. Evidence suggests that different subtypes of 19dels exhibit different survival outcomes to EGFR-TKI treatment. Whether patients harboring EGFR Leu747_Ser752 deletion (delL747_S752) as an uncommon subtype of 19dels benefit from EGFR-TKIs has not been investigated. BIM (B-cell chronic lymphocytic leukemia/lymphoma-like 1) deletion polymorphism is common in East Asian with EGFR-mutant non-small-cell lung cancer (NSCLC). Currently, the predictive role of BIM deletion polymorphism in patients with EGFR-mutant NSCLC treated with osimertinib remains debatable. Case Description: A 34-year-old female patient was diagnosed with stage IV lung adenocarcinoma (LUAD) harboring somatic EGFR del L747_S752 and germline BIM deletion polymorphism in August 2018. She obtained benefit from the front-line treatment of osimertinib lasting for 8 months. After progression from osimertinib, the patient received bevacizumab combined with platinum-doublet chemotherapy, stereotactic radiosurgery plus osimertinib and crizotinib, anlotinib, and a programmed cell death-1 inhibitor sintilimab plus bevacizumab and docetaxel. She succumbed to her disease in June 2020 with an overall survival of 23 months. Conclusions: Our work suggests that osimertinib might be a compromised treatment option for NSCLC patients with somatic EGFR delL747_S752 and germline BIM deletion polymorphism. Development of more effective regimens are needed for this small subset of NSCLCs.

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