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ADC Drugs For Non-small Cell Lung Cancer
EP38622
Poster Title: ADC Drugs For Non-small Cell Lung Cancer
Submitted on 12 Apr 2022
Author(s): Sunny Fang
Affiliations: Biopharma PEG Scientific Inc.
Poster Views: 327
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Poster Information
Abstract: 1. The NSCLC and ADC
Few lung cancer patients benefit from targeted therapy or immunotherapy, and most lung cancer patients still develop acquired drug resistance. Therefore, research on alternative treatment means is extremely important. In recent years, with the rapid development of ADC (Antibody-drug Conjugates), it has also shown good efficacy in the field of lung cancer, mainly involving targets including Her2, Her3, TROP-2, etc.

2. HER2 ADC
In the field of lung cancer, the ADC drugs under research, HER2 (human epidermal growth factor receptor 2, also known as ERBB2) target is the most.

HER2 ADC also dominates the entire development of ADC drugs, but Her2 mutations are mainly concentrated in the field of breast cancer and gastric cancer. The mutation rate of lung cancer is low, and research progress is naturally slow. However, HER2 mutations are closely related to increased disease recurrence and poor prognosis. The clinical treatment of these patients is also difficult and worth studying.

According to statistics, about 3% of NSCLC patients have HER2 mutations, of which 90% are exon 20 mutations, as shown in the figure below.

Figure 2 Schematic diagram of HER2

Among the ADC drugs targeted Her 2, the fastest progress is T-DM1 and DS-8201 (T-DXd).

>> T-DM1

T-DM1 is an ADC drug from Roche with a drug antibody ratio (DAR) of 3.5. Trastuzumab, a monoclonal antibody that targets HER2, was selected for the antibody. The linked chemotherapy drug is Maitansine which inhibits microtubule aggregation. The side effects of Maitansine are so severe that it is almost no longer used in clinic. However, through the design of ADC drug molecules, an antibody-coupling structure is formed, which can be locally released on tumor cells, which can exert a good anti-cancer effect and effectively reduce toxicity. At present, it has become the standard regimen for second-line treatment of HER2-positive breast cancer.
Summary: Despite the rapid progress of targeted therapy in the field of NSCLC (non-small cell lung cancer), there are still unmet needs. This article summarizes the latest progress in the targeted therapy of Her2, Her3 and Trop-2 in NSCLC.References: [1] Reuss JE et al.Clinical Lung Cancer, Vol. 22, No. 6, 483–499.
[2] Mishra, Rosalin,et al. "HER3 signaling and targeted therapy in cancer." Oncologyreviews 12.1 (2018).
[3] Mujoo, Kalpana,et al. "Regulation of ERBB3/HER3 signaling in cancer." Oncotarget5.21 (2014): 10222.
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