Instruct: Identify the main and secondary category of Arxiv papers based on the titles and abstracts
Query: Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor
  to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown   A tri-block nanoparticle (TBN) comprising of an enzymatically cleavable
porous gelatin nanocore encapsulated with gefitinib (tyrosine kinase inhibitor
(TKI)) and surface functionalized with cetuximab-siRNA conjugate has been
synthesized. Targeted delivery of siRNA to undruggable KRAS mutated non-small
cell lung cancer cells would sensitize the cells to TKI drugs and offers an
efficient therapy for treating cancer; however, efficient delivery of siRNA and
releasing it in cytoplasm remains a major challenge. We have shown TBN can
efficiently deliver siRNA to cytoplasm of KRAS mutant H23 Non-Small Cell Lung
Cancer (NSCLC) cells for oncogene knockdown; subsequently, sensitizing it to
TKI. In the absence of TKI, the nanoparticle showed minimal toxicity suggesting
that the cells adapt a parallel GAB1 mediated survival pathway. In H23 cells,
activated ERK results in phosphorylation of GAB1 on serine and threonine
residues to form GAB1-p85 PI3K complex. In the absence of TKI, knocking down
the oncogene dephosphorylated ERK, and negated the complex formation. This
event led to tyrosine phosphorylation at Tyr627 domain of GAB1 that regulated
EGFR signaling by recruiting SHP2. In the presence of TKI, GAB1-SHP2
dissociation occurs, leading to cell death. The outcome of this study provides
a promising platform for treating NSCLC patients harboring KRAS mutation.

1
The categories of this paper are: cs
29
The categories of this paper are: funct-an
36
The categories of this paper are: cmp-lg
32
The categories of this paper are: atom-ph
3
The categories of this paper are: physics
34
The categories of this paper are: chem-ph
11
The categories of this paper are: hep-lat
7
The categories of this paper are: hep-th
13
The categories of this paper are: quant-ph
0
The categories of this paper are: hep-ph
2
The categories of this paper are: math
26
The categories of this paper are: bayes-an
16
The categories of this paper are: stat
15
The categories of this paper are: nucl-ex
31
The categories of this paper are: ao-sci
17
The categories of this paper are: q-fin