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*For medical professionals only
In the face of the "king" of cancer - pancreatic cancer, are we really helpless?
Pancreatic cancer has always been known as the "king" of cancer, and the number of deaths due to pancreatic cancer in the world reached 466003 in 2020, ranking seventh in the number of deaths from malignant tumors in the world that year [1].
At present, the incidence and death rate of pancreatic cancer are increasing year by year, which has become an urgent treatment problem
in the field of malignant tumors.
Although surgery and traditional chemotherapy have improved the prognosis of pancreatic cancer patients to some extent, it is far from meeting the survival needs
of clinical pancreatic cancer patients.
Due to the special tissue structure characteristics and tumor microenvironment of pancreatic cancer, it has been difficult to achieve breakthroughs
in drug treatment for decades.
In April 2022, irinotecan liposomes were approved for marketing in China, successfully breaking the dilemma that no treatment drugs for pancreatic cancer have been approved in the past 23 years
.
On the occasion of "World Pancreatic Cancer Day", the medical community invited Professor Liu Liang to give an in-depth explanation of the drug selection and treatment progress
of pancreatic cancer.
Professor Liu Liang's wonderful video
Like walking on thin ice, pancreatic cancer treatment is in prison
Professor Liu Liang elaborated: "According to the World Cancer Report 2020, there are about 125,000 new cases of pantactic cancer in China every year, which is the eighth most common cancer in China[2].
Although its incidence is not the highest tumor, the survival situation is worrying, in patients with metastatic pancreatic cancer, the median survival is basically about 6 months, and the 5-year survival rate is only 5%-10% [3].
In terms of its survival rate or mortality, pancreatic cancer is indeed a change, known as the 'king'
of cancer.
Professor Liu Liang talked about the current status of pancreatic cancer treatment: "At present, the treatment methods for pancreatic cancer are not satisfactory
.
Surgical resection has been the mainstay of treatment for solid tumors, including pancreatic cancer, and is the 'only' hope
for long-term survival for pancreatic cancer patients.
However, the clinical symptoms of pancreatic cancer are not typical, and its incidence lacks specific indications, so the means of early screening and prevention are very limited
.
Most patients present in the middle to advanced stages, and only 15% to 20%
have the opportunity to undergo surgical resection.
Secondly, pancreatic cancer is a relatively special tumor
from both histopathological and molecular pathological perspectives.
Chemotherapy is the cornerstone of the current treatment of pancreatic cancer, and the existing first-line and second-line chemotherapy drugs for pancreatic cancer are mainly gemcitabine, fluorouracil, capecitabine and tigio
.
The new drugs are oxaliplatin, albumin paclitaxel, and irinotecan, and there is a very short choice of drugs
.
On this basis, pancreatic cancer has a certain degree of resistance and drug resistance to existing chemotherapy drugs due to the particularity of its tumor lesions, resulting in pancreatic cancer facing great challenges in drug treatment and urgent need for more effective treatment
.
Radiotherapy, one of the three traditional treatments, can improve pain with radiotherapy in some patients, but there is no high-level evidence-based medical evidence that patients benefit from survival
.
Professor Liu Liang concluded: "Pancreatic cancer has a high degree of malignancy, the existing treatment methods are lacking, and the available treatment efficacy is not satisfactory
.
There are huge and unmet clinical needs in the clinic, which makes the diagnosis and treatment of pancreatic cancer on thin ice, and more effective treatment drugs are urgently needed to break this dilemma
.
”
The "king" of cancer, why is pancreatic cancer so difficult to treat?
Professor Liu Liang said, "The three traditional treatment methods of surgery, chemotherapy and radiotherapy have failed to meet the treatment needs of pancreatic cancer patients, and targeted therapy and immunotherapy have achieved little
effect in the field of pancreatic cancer diagnosis and treatment in recent years.
There are certain limitations in targeted therapy for pancreatic cancer, one of which is that there are only a few
targeted therapy drugs for pancreatic cancer.
Erlotinib is used as an EGFR inhibitor for the treatment of advanced unresectable or metastatic pancreatic cancer, and although positive results have been obtained in its study, it is relatively limited in prolonging patient survival and still does not meet the current clinical needs
.
Second, for targeted drugs such as PRAP inhibitors, NTRK inhibitors and AMG510 against KRAS G12C mutations, there are great limitations in the selection of populations
.
Currently, only 5% of pancreatic cancer patients benefit from targeted therapy [4].
In addition, immunotherapy, one of the five major anti-cancer treatments, is in the ascendant, but in the treatment of pancreatic cancer, none of the phase III studies have been successful, and almost all phase I to II studies have been broken and failed to achieve positive results
.
Therefore, immunotherapy such as PD-1 inhibitors, CTLA-4 inhibitors and dual immunotherapy, including cell therapy, tumor vaccine development, etc.
, can make breakthroughs in the treatment of pancreatic cancer, and there is still a long
way to go.
"
Pancreatic cancer is distinguished from other solid tumors in that its histological characteristics are that there are fewer cancer cells and more
interstitial components.
Professor Liu Liang gave a vivid explanation from the histology and cytology of pancreatic cancer: "In pancreatic cancer, fibrous connective tissue hyperplasia is obvious, about 80% of tumor tissue is composed of interstitial tissue, and the dense matrix of pancreatic cancer forms a barrier
similar to a fence.
First, the interstitial layer constructs a state of isolation from the outside world, which not only creates an environment for the tumor to promote its growth and invasion, but also prevents the transmission of drugs and the infiltration of immune cells [5-6], making it difficult for anti-tumor drugs to kill
tumors.
Second, the dense interstitium forms a situation of tissue hypertension, and the vascular density of pancreatic cancer is low, and the vascular perfusion is insufficient, resulting in ischemia and hypoxia in the tumor area, weakening the transport ability of the drug, and reducing the accumulation of drugs in the tumor tissue [5-6], such a harsh environment also contributes to the highly malignant characteristics
of cancer cells.
Professor Liu Liang clarified: "From the perspective of cytological characteristics, there are many other cells in the interstitial component, including fibroblasts, neutrophils, macrophages, T cells and B cells
.
These cells normally act as an immune barrier in the human body and resist external invasion, but in pancreatic cancer, they are modified by cancer cells to form a cancer-promoting phenotype
.
Therefore, due to the characteristics of the two levels of histology and cytology of pancreatic cancer, a tumor microenvironment with high pressure, ischemia, hypoxia and acid-base balance disorder has been formed, so that the malignant characteristics and malignant potential of cancer cells have been more and more 'experienced'
.
This has resulted in pancreatic cancer showing little benefit to existing treatment options
.
”
Innovation, irinotecan liposomes break through the shackles
Professor Liu Liang said: "At present, it is very difficult to find new drugs or targets, and innovative changes
need to be made on existing drugs.
On the one hand, drugs are needed to break through the tight barrier of pancreatic cancer and enter the inside of the
tumor.
On the other hand, after the drug enters the tumor, it improves its retention and kills cancer cells
relatively long-lastingly.
Irinotecan liposomes add nanoparticles
to the base layer of irinotecan.
Liposomes have good biocompatibility and polarity, which prevents irinotecan from being cleared and converted into an inactive form in plasma, and also avoids premature metabolism by the liver, making it stay in the systemic circulation longer, thereby prolonging the half-life; In addition, thanks to the modified nanoparticle size, the drug can reach a high osmotic and long retention state in the body and enter the tumor environment preferentially [7].
Irinotecan liposomes have achieved the characteristics of high retention and high lethality through scientific modification methods, which confirms the innovation and superiority
of its drugs.
In traditional drug chemotherapy, irinotecan liposomes have reached a new milestone breakthrough
.
Professor
Liu Liang also took us to review the NAPOLI-1 study [8]: "The results of the study show that irinotecan liposomes combined with 5-fluorouracil/calcium folinate (5-FU/LV) can significantly improve overall survival (OS) and progression-free survival (PFS)
in patients.
At the same time, the survival benefit of irinotecan liposomes in Asian populations was more significant
.
Based on the positive results of this study, many authoritative guidelines at home and abroad, such as CSCO, NCCN and ESMO, have unanimously recommended irinotecan liposomes +5 FU/LV as the second-line treatment option after gemcitabine as the basic treatment regimen, bringing new treatment hopes and solutions
to pancreatic cancer patients.
”
Cohesion, doctors and patients work together to fight pancreatic cancer
Speaking of the problem of early screening of diseases, Professor Liu Liang also carried out relevant science popularization to the general public and patients, for the general population, Professor Liu Liang suggested: "The first point is that due to the hidden onset of pancreatic cancer, the early symptoms are atypical
.
Therefore, when our body does not have very specific or obvious changes, we need to go to the hospital in time
.
The associated manifestations of early pancreatic cancer include abdominal pain or epigastric discomfort, weight loss and fatigue, diarrhea and indigestion, and jaundice [9].
The second point is to pay attention to high-risk groups, epidemiology shows that the incidence of pancreatic cancer is related to a variety of risk factors, family inheritance is one of the high-risk factors of pancreatic cancer, and people with a family history of pancreatic cancer, pancreatitis or other hereditary tumors have an increased
risk of cancer.
For patients who have already developed pancreatic cancer, Professor Liu Liang elaborated on two sets of encouraging diagnosis and treatment data in the past ten years: "In the first ten years, the five-year survival rate of pancreatic cancer was less than 5%, and in the past five years, the five-year survival rate has been significantly improved at home and abroad, exceeding 10%.
Of any malignancies, only pancreatic cancer has seen a breakthrough
that has multiplied its survival rate in the last five years.
Although this data is only a small step forward in numerical terms, it gives pancreatic cancer patients new hope
for survival.
In terms of the five-year survival rate for pancreatic cancer, it is expected to reach 20%
in the next five years.
At the same time, even if the survival rate of pancreatic cancer is extremely poor, the majority of patients should believe in science and actively treat, and the objective response rate (ORR) of most treatments can reach 30%-60%, even if the survival period is not significantly extended, the advanced quality of life of
patients can be improved to a certain extent through treatment.
Finally, Professor Liu Liang said, "Doctors are also actively seeking new treatments, applying some new therapeutic drugs and strategies, allowing patients to actively participate in or try clinical research, and jointly explore better comprehensive diagnosis and treatment strategies
for pancreatic cancer in the future.
" 。 To fight the malignant tumor of pancreatic cancer, doctors in various hospitals and departments need to cooperate sincerely, build a better multidisciplinary team, standardize diagnosis and treatment of patients, and manage the whole course of the disease, so as to jointly improve the survival rate of pancreatic cancer patients, improve the quality of life, and seek more ideal survival benefits.
Expert
profile
: Professor Liu Liang
Chief physician, doctoral supervisor
Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University
Author of the 2012 edition of "Clinical Diagnostic Standards for Pancreatic Cancer in China"
Author of the 2018 and 2020 editions of the Guidelines for the Comprehensive Diagnosis and Treatment of Pancreatic Cancer in China
Expert of the pancreatic cancer project team of the 2025 "National Big Science Program and Big Science Project"
Expert of the project team of "Research on Precision Medicine Development Strategy", Faculty of Chinese Academy of Sciences-National Natural Science Foundation of China
Member of the Pancreatic Cancer Quality Control Expert Committee of "National Cancer Center-National Cancer Quality Control Center"
Member of the American Society of Clinical Oncology (ASCO).
Member of the Japanese Cancer Society (JCA).
Member of Chinese Society of Clinical Oncology (CSCO).
Member of Pancreatic Cancer Professional Committee of Shanghai Anti-Cancer Association
Member of the Clinical Research Committee of Oncology Drugs of Shanghai Anti-Cancer Association
Member of the Digestive Disease Professional Committee of Shanghai Medical Association
Member of the Precision Medicine Professional Committee of the National Cancer Treatment Strategic Alliance
Deputy leader of China Precision Treatment Collaborative Group for Rare Mutation Tumors
References:
[1] Sung H,Ferlay J,Siegel RL,et al.
Global Cancer Statistics 2020:GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.
CA Cancer J Clin.
2021 May; 71(3):209-249.
[2] International Agency for Research on Cancer.
Latest global cancer data:Cancer burden rises to 19.
3 million new cases and 10.
0 million cancer deaths in 2020[J].
World Health Organization,2020.
[3] Oncologist Branch of Chinese Medical Doctor Association, Pancreatic Disease Expert Committee of China Association for the Promotion of International Exchange in Healthcare Care, Abdominal Oncology Expert Committee of China Medical Education Association.
Expert consensus on multidisciplinary comprehensive treatment model of pancreatic cancer in China (2020 edition)[J].
Journal of Clinical Hepatobiliary Diseases,2020,36(9):1947-1951.
)
[4] Marquart J，Chen EY，Prasad V .
Estimation of the Percentage of US Patients with Cancer Who Benefit From Genome-Driven Oncology［J］.
JAMA Oncol，2018，4（8）：1093-1098.
[5] Sclafani F,Iyer R,Cunningham D,et al.
Management of metastatic pancreatic cancer:Current treatment options and potential new therapeutic targets.
Crit Rev Oncol Hematol.
2015 Sep; 95(3):318-36.
[6] Oberstein PE,Olive KP.
Pancreatic cancer:why is it so hard to treat? Therap Adv Gastroenterol.
2013 Jul; 6(4):321-37.
[7] Steichen SD,Caldorera-Moore M,Peppas NA.
A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics.
Eur J Pharm Sci.
2013 Feb 14; 48(3):416-27.
[8] Wang-Gillam A,Li CP,Bodoky G,et al.
NAPOLI-1 Study Group.
Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy(NAPOLI-1):a global,randomised ,open-label,phase 3 trial.
Lancet.
2016 Feb 6; 387(10018):545-557.
doi:10.
1016/S0140-6736(15)00986-1.
Epub 2015 Nov 29.
Erratum in:Lancet.
2016 Feb 6; 387(10018):536.
[9] Medical Administration of the National Health Commission of the People's Republic of China.
Guidelines for the diagnosis and treatment of pancreatic cancer(2022 edition)[J].
Chinese Journal of Digestive Surgery,2022,21(9):1117-1136.
)
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform
