Lung cancer is a malignant tumor with extremely high mortality rate worldwide, and its hazard cannot be ignored. The high mortality rate of lung cancer is closely related to such factors as vague early symptoms, difficult diagnosis, and drug resistance in the treatment process. "Black Myth: Wukong" is an action role-playing game based on the China myth story of The Journey to the West. The Wukong in the game needs to adopt different fighting strategies against different enemies, which is the same as the individualized treatment strategy for different genetic variations in the treatment of lung cancer ^[1]. Eighty-one difficult has countless monsters and different difficulties.

Common gene mutation and its proportion in non-small cell lung cancer

The molecular variation spectrum of NSCLC patients is mainly reflected in adenocarcinoma, including common mutant genes epidermal growth factor receptor (EGFR, 45%–55%), KRAS (8%–10%) and anaplasticlymphomakinase (ALK, 5%–10%). The rare mutation genes ROS1 (2%–3%), MET (2%–4%), HER2 (2%–4%), BRAF (1%–2%) and RET (1%–4%), as well as the rare mutation genes NTRK(<1%), NRG1/2(<1%), and FGFR2(<1%), etc. The problem of drug resistance in the treatment of lung cancer is far from Wukong's eighty-one difficult's ability. The endless stream of drug resistance challenges and hundreds of millions of mutations of lung cancer patients in the treatment process have always been the main obstacle to the effect of treatment ^[2].

Resistance mechanism of EGFR-TKI therapy

"The right remedy to the case" should be taken against the drug resistance mechanism, and multi-gene detection should provide the basis for accurate treatment of cancer from the perspectives of targeting, chemotherapy and immunization. WuKong through multi-skill blessing and continuous fighting to find the enemy's weakness to defeat the devil is nothing more than so, BaiGujing three changes in an attempt to deceive tang's monk, but each time by the WuKong see through and beat. After multiple treatments, lung cancer cells can develop different drug resistance through different mechanisms. For example, in NSCLC treatment, EGFR gene mutation is a common driver gene mutation. After receiving EGFR-TKI treatment, NSCLC patients with EGFR mutation almost inevitably develop drug resistance. Only when new drug resistance mutations or other target-and off-target mutations are found through multi-gene detection can the "seventy-two metamorphoses" provide a more accurate treatment plan for lung cancer treatment.

 EGFR-TKI and resistance therapy

[Case Report] Most ALK-positive lung cancers develop ALK-independent resistance after treatment with next-generation ALK inhibitors, and treatment with next-generation ALK inhibitors, especially in the first-line treatment, may result in MET-driven resistance. Patients with acquired MET changes may obtain clinical benefits from treatment of ALK and MET ^[3].

MET-driven resistance therapy for ALK-positive lung cancer

In conclusion, with the deepening of medical research, gene sequencing and the development of precision medicine, there are more possibilities for personalized treatment of lung cancer, and targeted therapy precision treatment can prolong the survival of patients ^[4]. With the continuous progress and improvement of precision medicine, it has brought precise and effective targeted therapy for drug resistance treatment of lung cancer and more hope for the survival of patients, which is also like the struggle and growth of WuKong in "Black Myth: WuKong".

Precision Treatment Prolongs Patient's Survival

References

[1] Biomark Res. 2024 Feb 12;12(1):24.

[2] Annual Reviews.Nov 25, 2019;4:279-297

[3] Clin Cancer Res. 2020 Jun 1;26(11):2535-2545.

[4] JAMA Oncol. 2021 Apr 1;7(4):525-533.