Table 1.

Drug delivery systems targeting aberrant signal pathways in cancer cells

Inhibition sites	Agents (in clinic)	Targeting mechanisms	Application	Limitations	References
EGFR	Imatinib, panitumumab, nimotuzumab, cetuximab, Canertinib, PKI166, Lapatinib, erlotinib, Gefitinib, nilotinib, resveratrol, recombinant immunotoxin, cross linking antibodies	Inhibition of receptor‐specific ligand binding, blocking activation of receptor tyrosine kinases, blocking ATP binding to the intracellular TK domain, inhibition the phosphorylation of receptors and activation of signal transduction molecules downstream	Hepatocellular carcinoma, anaplastic thyroid cancer, head and neck squamous cell carcinoma, human colon adenocarcinoma, non‐small cell lung cancers	Neutropenia, thrombocytopenia, diarrhea, erythra	61
PI3K	XL147, PX866, GDC0941, Buparlisib, Idelalisib, NVP‐BeZ235	Antiproliferative, bind competitively and reversibly in the ATP binding pocket of the catalytic kinase domain, inhibiting p110δ lipid kinase α and β p110 isoforms	HER2‐amplified and PIK3CA mutated cancers, lung adenocarcinomas,	Insulin resistance, limited efficacy	9, 20
Akt/PKB	Perifosine, GSK690693, Triciribine, MK2206	Growth and invasiveness inhibition, apoptosis promotion	Cancers with AKT1 mutations and AKT1 and AKT2 amplifications	Insulin resistance, limited efficacy	19
mTOR	OSI027, AZD8055, NVP‐BeZ235, Rapamycin, Wortmannin	Anti‐proliferative activity	Breast cancer, lung cancer, prostate cancer, hamartomas	Minimal effects, limited efficacy	23, 24
Ras	Farnesyltransferase inhibitor, AFC	Inhibition of Ftase, ICMT, RCE1	Bladder cancer, head and neck cancers, astrocytic gliomas	Low activity, less targeting, toxicity	25
Raf	Sorafenib, Vemurafenib, ZM336372, AZ628, Raf265, AAL881, LBT613	Anti‐proliferative, anti‐angiogenic, pro‐apoptotic activities	Refractory solid tumors, renal cell carcinoma, hepatocellular carcinoma, thyroid carcinoma	Skin rush, diarrhea and hypertension	26
MEK/ERK	PD 098059, U0126, Ro 09‐2210, PD184352, PD0325901, Selumetinib, GDC‐0973, Refametinib, Trametinib, Pimasertib, Selumetinib	Inhibiting proliferation	Colorectal, pancreatic, liver, skin, and lung cancer, lymphoma	Diarrhea, asthenia, rash, nausea, and vomiting. blurred vision, acute neurotoxicity	31
MDM2	Nutlins, RITA, quilinos, spiro‐oxidoles, HL198C, benzodiazepines	Liberating p53 and leading to growth arrest and apoptosis	Refractory solid tumours, hematologic Neoplasms	p53 toxicity to normal tissues	28, 29
JAK/STAT	AUH‐6‐96, c‐Src siRNA, cucurbitacin B, andrographolide	Inducing programmed cell death, increasing cell cycle arrest and apoptosis, enhancing chemosensitivity	Hodgkin lymphoma, head and neck squamous cell carcinoma, pancreatic cancer	Toxicity to normal tissues	11
Wnt	Dickkopf‐1, 2,4‐diamino‐quinazoline, ICG‐001‐related analogs, NSC668036	Anti‐proliferation, immune therapy	Cancers of pancreas, stomach, liver, bile duct, breast, and cervix	Toxicity to normal tissues	12, 43
JNK	SP600125, JNK 401, semapimod, Bi‐78D3, JNKi1	Anti‐proliferation, induction of cell death	Hepatocellular carcinoma, myelogenous leukemia	Lack specificity and selectivity for the different JNK isoforms	10
IκB	Celastrol, BMS‐345541, parthenolide, wedelolactone, PS‐1145, MLN120B, KINK‐1	Inhibiting growth and inducing apoptosis, attenuating drug resistance	Breast cancer, lymphomas, multiple myeloma, melanoma cells	Toxicity to osteoclast and inhibiting bone resorption	45, 46, 50
NF‐κB	IκBα, parthenolide, H157I, bortezomib, MG132, PS‐34, SC‐236, DHMEQ	Chemosensitization and radiosensitization, attenuating drug resistance	Breast, lung, colorectal, pancreatic, ovarian, thyroid and prostate cancer and malignant glioma	Immune suppression and poor targeting	47, 50
p53	Pifithrin‐α and its derivatives, MDM2 inhibitors	Reducing side effects of radiotherapy and chemotherapy and sensitizing apoptosis	Skin cancer, hematologic neoplasms, colon carcinoma	Low efficiency, toxicity to normal tissues, undefined mechanism	14, 53