| Drug/ class | Mechanism of action | Characteristics and adverse effects |
| Tyrosine kinase inhibitors | ||
| Dasatinib, imatinib, nilotinib, erlotinib, sorafenib, sunitinib, crizotinib | Inhibit enzyme tyrosine kinase (TK) by competing with ATP for binding site on TK. TKs are enzymes causing ATP dependent tyrosine phosphorylation and affecting cell proliferation and signalling pathways. TKs include EGFR, PDGFR, VEGF and Insulin receptors, Src kinases, abl kinases etc. Overexpression of TKs is seen in cancers. |
High selectivity, efficacy and lower side effects. Used in CML, NSCLC and renal cell cancers; Adverse effects include diarrhea, myalgia, CCF, edema; Imatinib, nilotinib and dasatinib inhibit Abl, PDGFR, inhibits bcr-abl expression, useful in CML and GIST; Erlotinib inhibits EGFR related TKs; Sorafenib inhibits VEGF related TKs; Sunitinib inhibits VEGF and PDGFR TKs; Crizotinib inhibits insulin receptor related TKs |
| Interferon alpha | Stimulates T cells to attack cancer cells | Used to treat NHL, hairy cell leukemia, CML, renal cell cancers, melanoma, neuroendocrine tumors, Kaposi’s sarcoma; Adverse effects include immunosuppression causing infections, decreased WBC count, diarrhea, insomnia, mood changes, headache, blurred vision, flu-like symptoms, alopecia, rash |
| Gonadal hormone antagonists | Tamoxifen: SERM(selective estrogen receptor modulator) with estrogen antagonist action on breast, agonist on endometrium and bone; Toremifene: Derivative of tamoxifen, SERM; Raloxifene: SERM, estrogen antagonist on breast and endometrium, agonist on bone; Fulvestrant: SERD (Selective estrogen receptor downregulator), anti-estrogen with no agonist activity, high affinity competitive antagonist at ER alpha receptors; Flutamide: androgen receptor competitive antagonist | Tamoxifen: used in ER+ breast cancer to prevent recurrence after chemotherapy. May cause pulmonary embolism, stroke, endometrial hyperplasia and carcinoma, nausea, vomiting and hot flashes; Toremifene: same as tamoxifen; Raloxifene: Increased risk of venous thromboembolism, hot flashes, leg cramps; use same as other SERMs, does not cause endometrial hyperplasia or cancer; Fulvestrant: Used in ER+ breast cancer; Flutamide: Used in metastatic prostate carcinoma, adverse effects include hot flashes, gynecomastia, decrease in libido, impotence, cholestasis, hepatic failure from inhibition of mitochondrial electron transport |
| GnRH analogues | Both constant doses of GnRH agonists and antagonists will be antagonistic to GnRH and cause decreased FSH and LH in the long run. Agonists may cause an initial, temporary rise in FSH and LH; Agonists include goserelin, histrelin, leuprolide, triptorelin; Antagonists include degarelix | They are used in the treatment of prostate cancer; Adverse effects include hot flashes, gynaecomastia, decreased libido, fatigue, weight gain, edema, impotence, osteoporosis, glucose intolerance, hepatic failure rarely |
| Aromatase inhibitors | Inhibits enzyme aromatase that catalyzes the rate limiting step in estrogen synthesis | Anastrozole; Letrozole (more potent than anastrozole); Exemestane (steroidal); Aminoglutethimide (not used now, non-selective); They are used in advanced breast cancer; Adverse effects include hot flashes, nausea, diarrhea edema, dyspnea,vaginal dryness, osteoporosis, increased cholesterol, muscle and joint pains |
| Asparaginase | A bacteria derived enzyme that hydrolyzes L-asparagine to L-aspartic acid and ammonia in leukemic cells, resulting in the depletion of asparagine, inhibition of protein synthesis, cell cycle arrest in the G1 phase, and apoptosis in susceptible leukemic cell populations | Used in the treatment of leukemias like ALL and lymphomas; Adverse effects include hypersensitivity, bleeding, DVT, PE, leukopenia, acute pancreatitis, diarrhea, rash and flu-like symptoms |
| Proteasome inhibitors | Inhibit catalytic activity of proteasomes resulting in the inhibition of NFkB activity, altered degradation of cell cycle proteins, apoptotic proteins; endoplasmic reticulum stress, inhibition of angiogenesis and DNA repair. It results in apoptosis of cancerous cells. | They are used in leukemias, lymphomas, multiple myeloma and solid organ tumors (except bortezomib); Bortezomib: causes peripheral neuropathy; Carfilzomib: less adverse effects |
| Histone deacetylase inhibitors | Histone deacetylases (HDAC) inhibit gene transcription and regulate the activity of transcription factors and signalling molecules. HDAC inhibitors increase acetylation, hence stability of critical tumor suppressors and transcription factors such as p53 and RUNX3 | Vorinostat; Romidepsin/depsipeptide; Apicidin; Adverse effects include diarrhea, fatigue, nausea, PE, thrombocytopenia, granulocytopenia |
| Monoclonal antibodies | ||
| Rituximab | Monoclonal antibody to CD 20 on B cells, targets the cancerous cell so it can be killed by the immune system | Adverse effects of monoclonal antibodies include needle-site reactions, flu-like symptoms, pain, swelling, rash, flu-like symptoms, nausea, vomiting, diarrhea, CCF, HT, AMI, mouth ulcers, ILD, capillary leak syndrome causing shock and organ failure and cytokine storm; Trastuzumab is used in the treatment of HER 2 positive breast cancer and gastric cancers |
| Blinatumomab | Monoclonal antibody to CD 19 on leukemic B cells and CD3 on T cells, helping the t cells to kill the leukemic B cells | |
| Trastuzumab/Herceptin, humanized IgG1 | Monoclonal antibody to HER2 (ErbB2), causes ADCC, inhibits HER2 signaling | |
| Bevacizumab, humanized IgG1 | Monoclonal antibody to VEGF | |
| Cetuximab, chimeric human/murine IgG1 | Monoclonal antibody to EGFR (ErbB1) | |
| Immune checkpoint inhibitors | Immune checkpoint proteins such as PD1, PD L1 or CTLA4 on tumor cells bind to T cells and prevent tumor killing by T cells. Immune checkpoint inhibitors bind to the checkpoint protein like PD L1, allowing T cells to kill the tumor cells | PD 1 inhibitors include pembrolizumab, nivolumab and cemiplimab; PD L1 inhibitors include atezolizumab, avelumab and durvalumab; CTLA4 inhibitors include ipilimumab which is a monoclonal antibody; Adverse effects include rash, diarrhea, fatigue, itchiness, hepatitis, hypophysitis, myocarditis, nephritis, diabetes, pancreatitis, pneumonitis, muscle weakness, dyspnea |
| All-trans retinoic acid | Derivative of Vit A, it induces differentiation, cell-cycle arrest and apoptosis of leukemic cells. It forms complexes with nuclear receptors or RARs that promote transcription | Treatment of acute promyelocytic leukemia; Adverse effects include flu like symptoms, headache, depression, dry skin and mucosa, nausea, vomiting, rash, mouth ulcers, vision changes, edema, arrhythmias, hyperleukocytosis, leukostasis with blood clots, cheilitis and elevation of serum triglycerides and cholesterol |
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