ESMO 2024: Targeting the Root Cause of Cancers

One of the major barriers in treating cancer successfully is how much tumors differ from one another.¹ This is why treatment often requires diverse mechanisms of action that target unique tumor cell surface molecules, or biomarkers. This enables researchers to target cancer cells more precisely, offering the potential to improve treatment outcomes.²

At this year’s European Society for Medical Oncology (ESMO) conference, Amgen presented the latest data from its oncology pipeline and portfolio that shows how the company is exploring a wide array of targeted modalities, including precision oncology and targeted immunotherapy approaches, with the goal of bringing new medicines to patients.

“We’re at a pivotal moment in oncology drug development where we can leverage insights from the underlying biology of different tumors to develop medicines that target the root cause of disease,” said Jay Bradner, M.D., Executive Vice President, Research and Development and Chief Scientific Officer at Amgen. “Our data at ESMO reinforce our strategy to pursue modalities that aim to target unique biomarker targets that play a role in cancer progression in our fight against the world’s toughest cancers.”

Here are three ways that Amgen is leveraging novel mechanisms to target unique tumor cell biomarkers in the fight against difficult-to-treat cancers.

Addressing the KRAS G12C Mutation in Metastatic Colorectal Cancer

The KRAS G12C mutation is a challenging target found in various cancers, including metastatic colorectal cancer (CRC).⁴ Previously, this mutation posed significant treatment difficulties, underscoring the need for additional targeted therapies.^3,4 As part of Amgen’s comprehensive CodeBreaK global development program, we continue to fully explore KRAS inhibition in solid tumors including mCRC.

Leveraging STEAP1 in metastatic castration-resistant prostate cancer (mCRPC)

Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive form of prostate cancer that often becomes resistant to standard therapies, requiring new treatment strategies.^5,6 One unique mCRPC target biomarker that Amgen is focused on is STEAP1. Overexpression of this protein has been shown to contribute to tumor progression, resulting in poor survival outcomes for people with elevated levels of the protein.⁷ Amgen is developing an investigational bispecific T-cell engager as a potential targeted immunotherapy for prostate cancer. It has two STEAP1 binding sites and one site that is designed to bind to T cells to hopefully enable T-cell-mediated fighting of tumor cells with STEAP1 on their surface.

Targeting methylthioadenosine phosphorylase (MTAP)-deleted solid tumors

Approximately 15% of all solid tumors exhibit a loss of the gene methylthioadenosine phosphorylase (MTAP).⁸ This deficiency leads to the buildup of a substance known as MTA in tumor cells.⁸ MTA disrupts the function of a protein molecule, arginine methyltransferase 5 (or PRMT5), whose abnormal activity can drive tumor growth, survival and proliferation.⁹ As a result, PRMT5 is considered an exciting target for treating solid tumors. PRMT5 inhibitors have the potential to promote tumor cell death, while sparing normal cells that do not have the MTAP deletion.¹⁰ This could improve outcomes and minimize toxicity.¹⁰

Additional information on the presentations can be found in our press release here.

---

References

1. Tiwari, A., Trivedi, R. & Lin, SY. J Biomed Sci. 29, 83 (2022).
2. Hou J, He Z, Liu T, et al. Front Oncol. 2022;12:755053.
3. Min HY, Lee HY. Exp Mol Med. 2022;54(10):1670-1694.
4. Fakih MG, Salvatore L, Esaki T, et al. N Engl J Med. 2023;389:2125-39.
5. Zhang D, Weng H, Zhu Z, et al. Front Oncol. 2024;14:1378993.
6. Liang Y, Rong E, Qian J, et al. Prostate Cancer Prostatic Dis. 2022;25(2):327-335.
7. Scott RJ, Mehta A, Macedo GS, et al. Oncotarget. 2021;12(16):1600-1614.
8. Patro, C.P.K., Biswas, N., Pingle, S.C. et al. J Transl Med 20, 620 (2022).
9. Zheng J, Li B, Wu Y, et al. J Med Chem. 2023;66(13):8407-8427.
10. Villalona-Calero MA, Patnaik A, Maki RG, et al. J Clin Oncol. 2022;40. TPS3167-TPS3167.