• uncontrolled and undifferentiated cell growth due to c-somal abnormalities
• tumor stem cells reside within a tumor 

• formed by genetically unstable cells
• apoptosis does not occur 
• resistant to chemotherapy and radiotherapy

• sex, age, race, genetics
• environmental = most important
• ionizing radiation
• chemicals
• viruses

cellular genes that code for growth factors

• malignancy can occur if uncontrolled

• code for factors that prevent cell growth
• i.e p53 gene
• Deleted/mutated can give rise to neoplastic cells (p53 mutated in lung, liver, breast, colon ca

• early detection is key
• almost 50% patients cured
• Advanced disease: Chemotherapy and radiotherapy before surgery

Chemotherapy used for:

1. Advanced Disease: no other treatment possible. Chemo alone. Metastatic disease. Improve QOL
2. Localized Disease: Neo-Adjuvant therapy. Other treatments available but not totally effective. Anal, bladder, esophageal, laryngeal cancer
3. Adjuvant Therapy: Surgery + Radiation. ↓ systemic and local effects and improve pts survival. Breast, lung, colon, gastric, Wilm's tumor, astrocytoma

1. G0: Quiescence, cell not actively dividing
2. G1: (40%) Synthesis of components for DNA synthesis. Cell decides whether to continue through the cell cycle at R
3. S (39%): DNA synthesis occurs
4. G2: (19%): preparation for mitosis
5. M: (2%) Mitosis and cell division

Antimetabolites

(stop cells making the building blocks of DNA) Methotrexate, 6MP, 5FU, etc. )

• Agents binding to DNA
• Stop DNA synthesis
• Alkylating agents, antitumor antibiotics, platinum compounds, miscellaneous others

• Microtubule inhibitiors
• stop cells making components needed to seperate
• Vinca alkaloids (Vinblastine, vincristine, vinrelbine)
• Paclitaxel

• maximal cell kill with minimal toxicity
• broader range on interaction of drug-cancer
• prevents/slows development of resistance
• efficacy: each drug should be efficient
• Toxicity: combination should not include similar toxic drugs
• scheduling: treatment-free intervals just long enough to provide tissue recovery
• interaction: biochemical, PK, and molecular interactions minimal 
• Dosing: avoid arbitrary dose changes 

• Relationship between dosing and clinical efficacy has been established
• 3 approaches to effective dosing: (need to reach level just below toxic)
  1. Dose escalation
  2. ↓ interval
  3. Sequential dosing (no gap between peaks)

• No response with drug therapy indicates towards a primary resistance. 
• Malignant melanoma, renal cell cancer and brain cancers
• had been blamed on loss of p53 tumor suppressor gene

• In response to exposure to chemotherapeutic agent
• usually a multdrug resistance occurs
• increased expression of MDR1 gene in certain tumors 
• cell learns to efflux, metabolize, etc durg

• Platinum inhibited growth of E. Coli
• kill cancer cells in all stages if the cell cycle
• all platinum analogues cleared by kidneys
• Oxaliplatin is 3rd generation and used as FOLFOX regimen for metastatic colorectal cancer
  • neuropathy may occur (cold triggered) reversible as compared to cisplatin

• Dose related
• bone marrow, GIT and reproductive systems most effected (rapid cell division)
• severe nausea and vomiting
• injection abscess and induration
• Carcinogenic

• combination of Oxaliplatin, 5FU, & Leucovorin 
• used for metastatic colorectal cancer

• methotrexate is folic acid analog
• binds DHFR, inhibits production of THFR and formation of cellular proteins needed by Ca cells to grow
• given intrathecal, oral or IV
• Renal excretion
• myelosupression, immunosuppression, neutropenia, thrombocytopenia 

• translocation of this c-some is inhibited in CML
• translocation causes formation of a Fusion protein which is present in 95% of pts with CML

• over expressed in some tumors
• activation results in cellular events such as cell growth, proliferation, invasion and metastasis, angiogenesis
• Cetubximab is a monoclonal antibody that acts against EGFR