CANCER CHEMOTHERAPPY (GENERAL INFORMATION)

CANCER--->over growth of cells

    

IT IS A DISEASE CHARACTERIZED BY A DEFECT IN THE NORMAL CONTROL MECHANISMS THAT GOVERN CELLS

• CELL SURVIVAL
• PROLIFERATION
• DIFFERENTIATION

HOW DOES A CANCER CELL PRESENT TO YOU?

Neoplastic Transformed cells usually express

• Cell surface antigens (THAT WILL BE OF NORMAL FETAL TYPE)
• Display apparent immaturity(take the example of cells in LEUKEMIA)
• Qualitative or Quantitative CHROMOSOMAL abnormalities

IF I TAKE OUT EVERYPERSON KNOWN TO ME AND SCREEN THEM FOR CANCER CELLS INDIVIDUALLY I WILL GET MINIMUM OF 5 TO 8 CANCER CELLS BUT THE ONLY REASON WE ARE SAFE BECAUSE THEY ARE NOT  ACTIVATED ONCE IF THEY GET ACTIVATED 

• The mother of all cancer cells called TUMOR STEM CELLS
• These cells reside within the tumor mass
• Retain the ability to undergo rapid transformation and repeated cycles of proliferation WHY? (stem cells)
• Migrate to distant sites to colonize various organs(METASTASIS)

So by conclusion we can say that TUMOR STEM CELLS have the property of

• COLONY FORMING ABILITY
• GENETIC INSTABILITY

DO YOU KNOW THE ROOT CAUSE FOR DRUG RESISTANCE IN CANCER it is the GENETIC INSTABILITY

WHICH ALLOWS THE TUMOR CELLS TO BECOME RESISTANT TO CHEMO AND RADIOTHERAPHY

CAUSES OF CANCER

The incidence,geographic distribution and behaviour of specific types of cancer are related to multiple factors including

• SEX
• AGE
• RACE
• GENETIC PREDISPOSITION
• EXPOSURE TO ENVIRONMENT CARCINOGEN

OUT OF THESE ALL ENVIRONMENTAL EXPOSURE IS OF PRIME IMPORTANCE

                                          

SEVERAL VIRUSES HAVE BEEN IMPLICATED IN THE ETIOLOGY OF VARIOUS HUMAN CANCERS

• HBV(Hepatitis B)HCV(Hepatitis C)

Hepatocellular cancer

• HIV(Hodgkin and Non Hodgkin lymphomas)
• HPV(Cervical,penile and oropharyngeal head and neck cancer)
• EPSTEIN BARR VIRUS (nasopharyngeal cancer)

SO HOW DOES THE CANCER GROW 

• ONCOGENES ACTIVATION
• INHIBITING APOPTOSIS (a programmed cell death)

When it comes to apoptosis and cell death theres comes a picture in our mind about a class of genes called TUMOR SUPRESSOR GENES 

• THEY ARE EITHER DELETED OR MUTATED GIVING RISE TO NEOPLASTIC PHENOTYPE

HERE COMES THE GUARDIAN ANGEL OF GENOME 

THE P53

THIS GENE SUPRESS THE MALIGNANT TRANSFORMATIONS

P53 IS MUTATED IN UP TO 50% OF ALL HUMAN SOLID TUMORS including liver,breast,colon,lung,cervix,bladder,prostate and skin
                          STRUCTURE OF P53

                        

CANCER TREATMENT MODALITIES

To be very honest these are the most toxic drugs 

These anticancer drugs either kill cancer cells or modify there growth

• CHEMOTHERAPY
• RADIOTHERAPHY
• SURGERY

CHEMOTHERAPHY

PRESENTLY USED IN 3 MAIN CLINICAL SETTINGS

1. Primary induction treatment for advanced cancers for which there is no other effective treatment approaches
2. NEOADJUVANT treatment for patients who present with localized disease for whom local form of therapy such as surgery or radiation or both are inadequate by themselves
3. Adjuvant treatment to local methods of treatment,including surgery,radiation therapy or both

LETS LEARN WHAT IS PRIMARY CHEMO AND NEOADJUVANT AND ADJUVANT AND THEIR GOALS

• PRIMARY CHEMO -->So when u have a advaned cancer means a cancer which is highly metastized and no alternative methods are there to treat this the main approach
• GOALS--

1. Remove tumor related symptoms 
2. improve overall quality of life 
3. prolong time of tumor progression

NEOADJUVANT CHEMOTHERAPY

Refers to the use of chemotherapy in patients who present  localized tumors for which local therpy exists such as SURGERY  

• GOALS--

1. Reduce the size of primary tumor so that the surgical resection can be made easier and more effective 
2. SUPPOSE A PATIENT HAS RECTAL and LARYNGEAL cancer ,the administration of chemotherapy prior to surgery can SPARE THE VITAL ORGANS 
3. Additional chemo is given 4 to 5 months after surgery has been performed 

ONE OF THE PRIME ROLES FOR CANCER CHEMO IS AN ADJUVANT TO CHEMOTHERAPY WHICH IS SURGERY

In this setting chemo is administrated after surgery 

THE GOAL--

1. Reduce the incidence of both local and systemic recurrence
2. improve overall survival of patients
3. Effective in prolonging both disease free survival and overall survival

ROLE OF CELL CYCLE KINETICS &ANTI CANCER EFFECT

L1210 MODEL 

L1210 IS A RAPIDLY GROWING LEUKAMIA WITH A HIGH % OF CELL SYNTH OF DNA MEASURED BY TRITATED THYMIDINE (labeling index)WHY? L1210 LEUKAMIA HAS A GROWTH FRACTION OF 100%

basic thing is if a particular dose of an individual drug leads to a 3-log kill of cancer cells and reduces the tumor burden from 10^power 10 to 10 power 7 so the same dose will reduce 10 power 5 to 10 power 2

                                 

SECOND MODEL 

GOMPERTZIAN MODEL

As L1210 the cell increases with time and exponential here it is reverse WHY?

According to this model when a patient of advanced tumor is treated generally

• THE TUMOR SIZE IS LARGE
• GROWTH FRACTION IS LOW 
• FRACTION OF CELLS KILLED IS SMALL why? only reasonable fraction of cancer cells will be active

SO BASED ON THESE DRUG COMBINATIONS AND DOSAGE ARE DECIDED

ROLE OF DRUG COMBINATIONS 

READ THE BELOW IMAGE CAREFULLY SINCE IT GIVES WHICH DRUGS TO BE GIVEN 

                            WHETHER CELL CYCLE SPECIFIC OR NOT SPECIFIC

                              

WHY COMBINATION THERAPY IS IMPORTANT THREE REASONS

1. IT PROVIDES MAX CELL KILL WITHIN THE RANGE OF TOXICITY TOLERATED BY THE HOST FOR EACH DRUG AS LONG AS DOSING IS NOT COMPROMISED
2. BROADER RANGE OF INTERACTION BETWEEN DRUGS AND TUMOR CELLS WITH DIFFERNT GENETIC ABNORMALITIES IN A HETEROGENOUS POPULATION
3. PREVENT OR SLOW THE CELLULAR DRUG RESISTANCE 
4. PRINCIPLES INVOVLED IN THIS 

• EFFICACY
• TOXICITY
• OPTIMUM SCHEDULING
• MECHANISM OF INTERACTION
• AVOIDANCE OF ARBITARY DOSE CHANGES 
• please go through all these points as they are of very prime important

DOSAGE FACTORS

AGAIN 3 FACTORS

1st -- DOSE ESCALATION (involves increasing the doses of the respective anti cancer agents )

2nd--REDUCING THE INTERVAL(between treatment cycles)

3rd--SEQUENTIAL SCHEDULING (single agents or combined drugs )

DRUG RESISTANCE 

FUNDAMENTAL PROMBLEM 

2 TYPES 

PRIMARY RESISTANCE (INHERENT RESISTANCE)

ACCQUIRED RESISTANCE (DUE TO DRUGS )

                                 

GUYS I HOPE I HAVE GIVEN EVERY BIT DETAIL ABOUT CANCER CHEMO PLEASE DO SHARE IT FOR MAXIMUM REACH

THANK YOU