Explore our comprehensive approach to cancer research
At Bristol Myers Squibb, we are driven by our passion to improve lives, with one of the most promising pipelines in the industry. Our cancer research approach stems from our deep understanding of disease biology and our belief in the importance of causal human biology. Expertise at the disease and molecular levels, coupled with insights from our industry-leading clinical and translational datasets, fuel the next wave of discovery and pipeline advances to bring meaningful new treatment options to patients. Explore our precision approach to cancer research below, and for more about our differentiated research platforms, visit our Protein Degradation and Cell Therapy hub pages.
Improve recognition of cancer cells
The immune system naturally defends and protects the body against infection, involving a complex network of cells and signaling molecules. Bristol Myers Squibb is investigating multiple pathways and targets with the aim of amplifying the ability of the immune system to recognize and eliminate cancer cells.
- Targeting the fucosyl-GM1 tumor-associated antigen is intended to improve the recognition of cancer cells by phagocytes and natural killer (NK) cells.1,2
- SIRPα is an inhibitory receptor expressed on macrophages and dendritic cells.1-3
- CD47, a protein found on the surface of cells, binds SIRPα, initiating an inhibitory signaling pathway that helps maintain immunotolerance to normal cells.1-3
- In cancer, overexpression of CD47 on the surface of tumor cells allows tumors to escape detection, acting as a “don’t eat me” signal, limiting the anti-cancer immune response.1-3
- Inhibition of the CD47-SIRPα signaling pathway is intended to improve the recognition and enhance phagocytosis of cancer cells by macrophages.4
The tumor microenvironment (TME) contains cells and signaling molecules that suppress an anti-tumor immune response. Bristol Myers Squibb is investigating ways to block the tumor’s ability to recruit immunosuppressive cell types to the TME and inhibit signaling that contributes to immunosuppression.
- is a protein found mainly on the surface of regulatory T cells (Tregs) within tumors and is a regulator of immune response.1,2
- CCR8 is upregulated on a highly immunosuppressive subset of Tregs in multiple cancer types.2,3
- Targeting CCR8 with an antibody to selectively eliminate Tregs within the TME has the potential to facilitate productive anti-tumor immunity.
- The release of IL-8 by cancer cells promotes immune evasion by recruiting immunosuppressive cell types to the TME, thereby reducing immune response against the tumor.1
- Prevention of IL-8 signaling is intended to inhibit the recruitment of immunosuppressive cell types to the TME.2
- ILT4 is an immunosuppressive molecule expressed in myeloid cells and present in the tumor microenvironment (TME).1
- Inhibition of the ILT4 receptor is intended to promote a proinflammatory response and result in subsequent cancer cell death.1
- JNK signaling promotes tumor development and plays a complex role in the regulation of key cellular activities in various cancer types, including cancer cell growth, differentiation and death.1
- Inhibition of JNK signaling is intended to target specific JNK-mediated cellular functions and result in cancer cell death.1
- TGF-β is a critical mediator of immuno-oncology resistance.1,2
- Neutralization of cytokines TGF-β1 and TGF-β3 is intended to decrease immune exclusion and increase effector cell function.1,2
Enhance effector cell function
Cancer cells can suppress effector cells (short-lived activated cells of the immune system), but these cells can also be modified to mount a cytotoxic attack. Bristol Myers Squibb is investigating ways to increase the ability of effector cells to act on cancer cells, direct cytotoxic activity toward cancer cells and engineer cell therapies that exhibit continued anti-cancer activity.
- Inhibitors of AHR are intended to block the activation of the AHR pathway—a pathway that promotes immunosuppression and immune cell dysfunction—leading to enhanced effector cell function.1,2
- Activated AHR is also associated with resistance to immune checkpoint blockade.2
- BCMA is a transmembrane protein that plays a key role in the proliferation, maturation and differentiation of B cells into plasma cells and is important for plasma cell survival.1
- BCMA can be overexpressed in cancer cells.2
- BCMA can be targeted using multiple types of anti-cancer therapeutics recognizing the BCMA receptor and subsequently killing the cancer cell.1,3,4
- CD33 is a protein that is expressed on acute myeloid leukemia cells.1
- CD33 can be targeted using anti-cancer therapies such as cell therapies, immune engagers and antibody drug conjugates, which recognize the antigen and subsequently kill the cancer cell.1
- CD96 is expressed on T cells and NK cells, sharing ligands with the TIGIT receptor and generating co-stimulatory or co-inhibitory signals.1
- Co-inhibition of CD96 and TIGIT is intended to restore effector cell function by blocking the inhibitory immune checkpoint signaling pathway.1
- CTLA-4 is an immune checkpoint receptor found on the surface of activated T cells.1,2
- Cancer cells use the CTLA-4 pathway to decrease T cell activation, proliferation and effector function—effectively turning “off” the immune response.3,4
- Bristol Myers Squibb pioneered the first approved immune checkpoint inhibitor, a monoclonal antibody targeting CTLA-4, which ushered in a historic era of harnessing the immune system to treat cancer and ignited exploration into the TME.
- Researchers are exploring strategies to optimize the CTLA-4 blockade by building on the existing CTLA-4 science through second- and next-generation compounds, with a goal of improving the risk-benefit profile of CTLA-4–directed therapy.5,6
- DGKs are a family of enzymes that modulate molecules that help regulate T cell activity.1
- Inhibition of DGKs is designed to improve T cell activity in cancer.1
- GPRC5D is a myeloma cell surface antigen overexpressed by cancer cells and associated with poor prognosis.1
- GPRC5D can be targeted using anti-cancer therapies such as cell therapies, immune engagers and antibody drug conjugates, which recognize the antigen and subsequently kill the cancer cell.1
- MAGEA4/8 is a highly prevalent antigen present in multiple solid tumors.1
- MAGEA4/8 can be targeted using anti-cancer therapies such as cell therapies, immune engagers and antibody drug conjugates, which recognize the antigen and subsequently kill the cancer cell.1
- Inhibition of NKG2A is intended to enhance effector cell function by blocking the inhibitory NKG2A immune checkpoint signaling pathway.1,2
- Prostate stem cell antigen (PSCA) is a glycoprotein that is overexpressed in prostate cancer cells and in other cancers including urothelial, pancreatic, renal and non-small cell lung cancer.1
- Expression of PSCA in prostate cancer is associated with advanced disease and poor prognosis.1
- PSCA can be targeted by anti-cancer therapeutics, such as T-cell engagers, facilitating cancer cell death.2
- TIGIT is expressed on T cells and NK cells, sharing ligands with the CD96 receptor and generating co-stimulatory or co-inhibitory signals.1-3
- Co-inhibition of TIGIT and CD96 is intended to restore effector cell function by blocking the inhibitory immune checkpoint signaling pathway.1-3
Target tumor-intrinsic pathways
Cancer cell growth and survival is dictated by molecular mechanisms within the tumor. Bristol Myers Squibb is working to leverage these various pathways to enhance cancer cell death, suppress mechanisms driving resistance to therapy, and enhance antitumor immunity.
- Aiolos and Ikaros
- Aiolos and Ikaros regulate gene expression in tumor cells and T cells and contribute to myeloma cell survival.
- The destruction of Aiolos and Ikaros, mediated through protein degradation, is intended to result in cancer cell death and stimulation of immune effector cells.1,2
- With targeted protein degradation, researchers are harnessing cells’ own machinery to degrade several whole new classes of proteins that were previously considered “undruggable.”
- Androgen receptors (AR) play a key role in prostate cancer cell proliferation, but increased AR expression and mutations lead to developed resistance to AR inhibitors.1
- The selective destruction of AR, mediated through protein degradation, is intended to inhibit the proliferation of cancer cells.2,3
- Inhibition of the BET pathway, which perpetuates tumor cell growth and survival, is intended to modulate genetic drivers of oncogenesis, leading to a decrease in tumor growth.1,2
- CK1α is a kinase that influences regulatory proteins involved in multiple signaling pathways important to cancer cells.1,2
- The selective destruction of CK1α, mediated through protein degradation, is intended to inhibit the proliferation of cancer cells.1,2
- FRα is a protein that is overexpressed on various cancer cell types, including ovarian, breast and lung cancers, but is minimally expressed in healthy cells.1
- Selectively targeting FRα is intended to help specifically deliver a therapeutic payload to cancer cells while minimizing the effect on healthy cells.
- ROS1 and NTRK gene alterations are oncogenic drivers of non-small cell lung cancer (NSCLC) and other advanced solid tumors.1, 2
- Targeting ROS1/NTRK is intended to block tumor growth by preventing crucial cancer cell functions and result in cancer cell death.1, 2
- SHP2 is an attractive therapeutic target due to its wide-ranging role in cancer growth and role in adaptive resistance to many targeted therapies.1
- SHP2 inhibition is intended to block tumor cell proliferation and survival and enhance antitumor immunity via:1-3
- Reduced tumor adaptive resistance to targeted therapies, including MAPK pathway inhibitors
- Increased CD8 T-cell proliferation and recruitment and decreased activity of immunosuppressive myeloid cells in the tumor microenvironment
Organic compounds that are relatively small in size, usually taken orally and easily absorbed by the body.
Autologous chimeric antigen receptor (CAR) T cell therapy reprograms immune cells to attack cancer.
Molecules that redirect the body’s immune response toward cancer cells.
“Masked” antibodies that are activated within the tumor microenvironment. Designed to limit activity—and toxicity—in healthy tissue.
Engineered antibodies that can bind to 2 different antigens.
By tethering a small molecule to a biologic, antibody-drug conjugates are engineered to deliver small molecules to targeted locations using biologic monoclonal antibodies as honing mechanisms.