Cancer cells have many ways to stop the immune system from recognizing and destroying them.1 Some of the biological components that may have a role in how the immune system identifies and attacks cancer cells include:
PD-1 and TIGIT: Receptors found at high levels on the surface of certain immune cells in various types of cancer, that are part of a pathway that can block recognition and destruction of cancer cells.1
Imagine cars — as our body’s immune cells — heading towards the Golden Gate Bridge to get to the other side in order to attack and destroy cancer cells.
As they approach the bridge, think of PD-1 and TIGIT like a stop sign and a red traffic light, respectively, that block the cars from crossing the bridge.
ADENOSINE: A compound that can accumulate in the area surrounding cancer cells, and is made by receptors found at high levels on cancer cells. It binds to other receptors on the surface of immune cells, which deactivates them from attacking cancer cells.2
Picture the cars are now driving on the bridge, but a thick, dense fog – this is like adenosine – rolls in and doesn’t allow the cars to see clearly to get across the bridge as they slowly roll to a stop, preventing them from attacking and destroying the cancer cells on the other side.
Other biological components are also involved helping cancer cells survive, such as:
HIF2α: Tumors often have low oxygen levels, and this regulator can promote growth of tumors in these conditions.3
In many cancers, more than one of these biological components are involved in preventing cancer cell death.4,5,6 Research is underway to determine whether stopping more than one of these biological components at the same time may improve the body’s ability to detect and destroy cancer cells.
Take a closer look at some different cancer types where a biology-driven, combination approach may lead to the development of new treatment approaches and help address unmet needs for people with cancer.
Non-small cell lung cancer
(NSCLC) represents about
Non-small cell lung cancer (NSCLC) represents about
85%
of all lung cancer diagnoses.7
Lung cancer is the:
2nd
most common
type of cancer7
#1
cause of cancer-
related deaths.7
Cancer treatment primarily depends on disease stage, which characterizes how big the tumor is and if it has spread throughout the body.8 One treatment approach is immunotherapy, which harnesses the body’s natural immune system to attack and destroy the cancer.1
Anti-PD-1s are a type of immunotherapy used to treat different stages of cancer.9 They are believed to work by blocking the PD-1 pathway and activating immune cells to attack cancer cells.1
In many people, however, the cancer can continue to grow even with anti-PD-1 treatment.1 Researchers are working to understand if combining multiple investigational medicines, that each target different immune-evading pathways, may lead to the development of new medicines to treat people with cancer.
Clinical trials are ongoing to understand if combining different investigational medicines to stop more than one biological pathway at the same time, with or without chemotherapy, may improve the ability of the immune system to detect and destroy cancer cells and lead to new treatment options.
Colorectal cancer (CRC) is any cancer that starts in the colon or rectum, collectively known as the large intestine.20
According to the American Cancer Society, CRC is the:
3rd
most common diagnosed cancer in the United States*20
2nd
leading cause of cancer-related deaths.20
Cancer treatment primarily depends on disease stage, which characterizes how big the tumor is and if it has spread throughout the body.8 One treatment approach is immunotherapy, which harnesses the body’s natural immune system to attack and destroy the cancer.1
Anti-PD-1s are a type of immunotherapy that are typically used at later stages of disease for people who have certain genetic changes in their cancer cells.21 They are believed to work by blocking the PD-1 pathway and activating immune cells to attack cancer cells.1
In many people, however, the cancer can continue to grow even with anti-PD1 treatment.22 Researchers are working to understand if combining anti-PD1 with other investigational medicines that each target different immune-evading pathways may lead to the development of new medicines to treat more people with metastatic cancer, or cancer that has spread to other parts of the body.
Clinical trials are ongoing to understand if combining different investigational medicines to stop more than one biological pathway at the same time, with or without chemotherapy, may improve the ability of the immune system to detect and destroy cancer cells and lead to new treatment options.
Upper gastrointestinal (GI) cancer includes cancers that occur in the stomach, esophagus (the tube that carries food and drinks from the throat to the stomach) and gastroesophageal junction (where the esophagus connects to the stomach).24
According to the National Cancer Institute, upper GI cancers are the:
2nd
most common cause of death among digestive system cancers.24
They have poor 5-year survival rates when diagnosed in later stages.29
Cancer treatment primarily depends on disease stage, which characterizes how big the tumor is and if it has spread throughout the body.8 One treatment approach is immunotherapy, which harnesses the body’s natural immune system to attack and destroy the cancer.1
Anti-PD-1s are a type of immunotherapy that are typically used at later stages of disease, including for people who have certain genetic changes in their cancer cells.30,31 They are believed to work by blocking the PD-1 pathway and activating immune cells to attack cancer cells.1
In many people, however, the cancer can continue to grow even with anti-PD-1 treatment.32,33 Researchers are working to understand if combining multiple investigational medicines, that each target different immune-evading pathways, may lead to the development of new medicines to treat people with cancer.
Clinical trials are ongoing to understand if combining different investigational medicines to stop more than one biological pathway at the same time, with or without chemotherapy, may improve the ability of the immune system to detect and destroy cancer cells, and lead to new treatment options.
References:
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2. Ohta, Akio. “A metabolic immune checkpoint: adenosine in tumor microenvironment.” Frontiers in immunology 7 (2016): 109.
3. Moreno Roig, Eloy, et al. “Prognostic role of hypoxia-inducible factor-2α tumor cell expression in cancer patients: a meta-analysis.” Frontiers in oncology 8 (2018): 224.
4. Akinleye, Akintunde, and Zoaib Rasool. “Immune checkpoint inhibitors of PD-L1 as cancer therapeutics.” Journal of hematology & oncology 12.1 (2019): 92.
5. Ge, Zhouhong, et al. “TIGIT, the next step towards successful combination immune checkpoint therapy in cancer.” Frontiers in Immunology 12 (2021): 699895.
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19. “How Chemotherapy Drugs Work.” American Cancer Society, November 2019. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/how-chemotherapy-drugs-work.html
20. “About Colorectal Cancer.” American Cancer Society, June 2020 & January 2023. https://www.cancer.org/cancer/colon-rectal-cancer/about.html
21. “Treating Colorectal Cancer.” American Cancer Society, June 2020. https://www.cancer.org/cancer/colon-rectal-cancer/treating.html
22. Makaremi, Shima, et al. “Immune checkpoint inhibitors in colorectal cancer: challenges and future prospects.” Biomedicines 9.9 (2021): 1075.
23. Hajizadeh, Farnaz, et al. “Adenosine and adenosine receptors in colorectal cancer.” International immunopharmacology 87 (2020): 106853.
24. “Introduction to UGI Cancer.” National Cancer Institute. https://training.seer.cancer.gov/ugi/intro/.
25. “What is Stomach Cancer?” American Cancer Society. https://www.cancer.org/cancer/types/stomach-cancer/about/what-is-stomach-cancer.html.
26. “Adenocarcinoma.” National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/adenocarcinoma.
27. “Esophageal Cancer” National Cancer Institute: MyPART. https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-digestive-system-tumors/esophageal.
28. Then, Eric Omar, et al. “Esophageal Cancer: An Updated Surveillance Epidemiology and End Results Database Analysis.” World Journal of Oncology. 11 (2020): 55-64.
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33. Voutsadakis, Ioannis A. “A systematic review and meta-analysis of PD-1 and PD-L1 inhibitors monotherapy in metastatic gastric and gastroesophageal junction adenocarcinoma.” Euroasian journal of hepato-gastroenterology 10.2 (2020): 56.
34. Wang, Daijun, et al. “Role of CD155/TIGIT in digestive cancers: promising cancer target for immunotherapy.” Frontiers in Oncology 12 (2022).
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36. Kono, Yusuke, et al. “Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients.” BMC cancer 20.1 (2020): 1-9.
37. Wang, Peipei, et al. “Increased coexpression of PD-L1 and TIM3/TIGIT is associated with poor overall survival of patients with esophageal squamous cell carcinoma.” Journal for Immunotherapy of Cancer 9.10 (2021).
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39. Chen, Yen-Hao, et al. “CD73 promotes tumor progression in patients with esophageal squamous cell carcinoma.” Cancers 13.16 (2021): 3982.
Arun Tholudur is SVP, Pharmaceutical Development & Manufacturing at Arcus. We sat down with him to discuss his love for playing cricket, his experience playing on the Masters Cricket USA National Cricket Team, and how lessons he’s learned from the sport apply to his work here at Arcus.
To evaluate the growing number of treatment options for cancer efficiently and rigorously, we need to rethink the way we approach early clinical trials.