RAS: Past, Present, and Future

Advancements in Cancer Research, volume 153, provides an overview of the biology, biochemistry, and approaches to therapeutically target the RAS oncoprotein, the most frequently mutated oncogene family in human cancers. The approval of the first direct RAS inhibitor (sotorasib) for treating non-small cell lung cancers harboring KRAS(G12C) mutations highlights the pharmacological tractability of RAS.

Format: Hardback
Length: 356 pages
Publication date: 04 February 2022
Publisher: Elsevier Science Publishing Co Inc

Advancements in Cancer Research, volume 153, presents a comprehensive and timely review of the biology, biochemistry, and emerging therapeutic strategies targeting the RAS oncoprotein, the most frequently mutated oncogene family in human cancers. In 2021, a significant milestone was achieved with the approval of the first direct RAS inhibitor (sotorasib) for the treatment of non-small cell lung cancers harboring KRAS(G12C) mutations. This approval underscores the fact that RAS, once considered "undruggable," is now amenable to pharmacological intervention. This volume offers a comprehensive overview of ongoing efforts to develop innovative approaches torapeutically target oncogenic RAS. Additionally, readers will find in-depth reviews exploring the historical background and extensive research endeavors aimed at understanding the biochemistry and oncogenic activities of RAS in human cancers.

The RAS oncoprotein is a crucial driver of cancer development, as it plays a pivotal role in regulating cellular growth, survival, and proliferation. It is mutated in a significant fraction of human cancers, including lung, colorectal, pancreatic, and breast cancers. The approval of sotorasib for the treatment of KRAS(G12C)-mutated non-small cell lung cancers represents a significant breakthrough in cancer therapy. This drug targets the RAS signaling pathway, which is activated by mutations in RAS genes. By inhibiting RAS, sotorasib can suppress cancer cell growth and proliferation, leading to improved patient outcomes.

The development of sotorasib was driven by extensive research efforts aimed at understanding the biology and function of RAS. Researchers have identified specific mutations in RAS that are associated with cancer development and have developed targeted therapies to inhibit these mutations. Sotorasib is the first RAS inhibitor to be approved for the treatment of cancer, and it has the potential to revolutionize the way we approach cancer therapy.

In addition to sotorasib, there are ongoing efforts to develop other RAS inhibitors and targeted therapies for RAS-mutated cancers. These efforts include the development of small molecule inhibitors that specifically target RAS proteins, as well as the use of immunotherapies and gene therapies to target RAS-driven tumors.

The understanding of the biology and function of RAS has also led to significant advances in our understanding of cancer development and progression. RAS mutations can activate multiple signaling pathways, including the PI3K/AKT/mTOR pathway, which is a key driver of cancer cell growth and survival. By targeting these signaling pathways, researchers can develop more effective therapies that target multiple cancer cells and improve patient outcomes.

In conclusion, the approval of sotorasib for the treatment of KRAS(G12C)-mutated non-small cell lung cancers highlights the potential of RAS as a therapeutic target. The development of additional RAS inhibitors and targeted therapies for RAS-mutated cancers is ongoing, and these efforts have the potential to revolutionize the way we approach cancer therapy. Continued research and development in this field will lead to improved patient outcomes and a better understanding of cancer biology.

Weight: 450g
Dimension: 229 x 152 (mm)
ISBN-13: 9780128244852