A radiologist's guide to novel anticancer therapies in the era of precision medicine

Abstract

Novel anticancer agents have replaced conventional chemotherapy as first line agents for many cancers, with continued new and expanding indications. Small molecule inhibitors act on cell surface or intracellular targets and prevent the downstream signaling that would otherwise permit tumor growth and spread. Anticancer antibodies can be directed against growth factors or may be immunotherapeutic agents. The latter act by inhibiting mechanisms that cancer cells use to evade the immune system. Hormonal agents act by decreasing levels of hormones that are necessary for the growth of certain cancer cells. Cancer therapy protocols often include novel anticancer agents and conventional chemotherapy used successively or in combination, in order to maximize survival and minimize morbidity. A working knowledge of anti-cancer drug classification will aid the radiologist in assessing response on imaging.

Keywords: Cancer; Chemotherapy; Hormonal agents; Immune checkpoint; Immunotherapy; Molecular therapy; Targeted therapy.

Fig. 1

VEGF inhibitors such as bevacizumab and ziv-aflibercept are antibodies that bind to VEGF and prevent its action on the receptor. VEGFR inhibitors such as axitinib and pazopanib block the VEGF receptor and prevent downstream signaling.

Fig. 2

ALK inhibitors bind to the ALK receptor and prevent downstream signaling through the PI3K, JAK and Ras pathways.

Fig. 3

ROS inhibitors bind to the cell surface ROS and prevent downstream signaling.

Fig. 4

BCR-ABL inhibitors prevent ATP from binding to the BCR-ABL protein and thereby prevent phosphorylation of its substrate. This leads to cessation of downstream signaling.

Fig. 5

PDGFR inhibitors bind to the PDGF receptor and prevent downstream signaling that decreases several processes such as cell proliferation /survival, and collagen and actin formation.

Fig. 6

PARP inhibitors inhibit repair of single strand DNA breaks. While BRCA proficient cells are able to repair these breaks, in BRCA deficient cells this leads to double strand DNA breaks and cell death.

Fig. 7

EGFR inhibitors such as cetuximab and panitumumab are antibodies that bind to and inhibit EGFR. Small molecule EGFR inhibitors such as gefitinib and afatinib block the receptor and prevent downstream signaling.

Fig. 8

Raf, MEK, PI3K and mTOR inhibitors bind to their respective targets and block signaling in the PI3K and Ras pathways.

Fig. 9

BTK inhibitors bind to the intracellular signaling protein BTK and block its downstream activation.

Fig. 10

CDK inhibitors block cell cycle and arrest it at the G1 phase.

Fig. 11

HER2 inhibitors such as trastuzumab and pertuzumab are antibodies that bind to and inhibit the HER2 receptor. Small molecule HER2 inhibitors such as neratinib and lapatinib block the receptor and prevent downstream signaling.

Fig. 12

PD-1 and PD-L1 inhibitors block the inhibitory effects of these receptors at the T-cell and tumor cell interface. CTLA-4 inhibitors block the inhibitory effects of CTLA-4 at the T-cell and antigen presenting cell interface.